A
Absorption, see Dietary copper Acelp,
copper detoxification, 577 gene targets, 482 structure and function, 577
Aceruloplasminemia, clinical features, 25, 190
Actin, see F-actin AD, see Alzheimer's disease Albumin, copper binding, 9,11,
189,344 ALS, see Amyotrophic lateral
sclerosis Alzheimer's disease (AD),
amyloid-~ copper role, 26, 270, 289,311
brain lesion characteristics, 307,308
metal ion homeostasis, 309-311 oxidative metabolism, 311 presenilin gene mutations, 307
am! cluster, Streptomyces, 515 Amicyanin,
crystal structure refinement with molecular dynamics, 95
molecular modeling of protein interactions, 92
Amyloid-~, copper,
Alzheimer's disease ROLE, 270,289,311
589
Index
transport, 270, 289, 297 precursor protein,
antioxidant responses, 309 copper homeostasis role, 309 copper reduction, 309 domains, 308 functions, 308, 309
Amyotrophic lateral sclerosis (ALS),
apoptosis in neurodegeneration, 286-288
copper chelators in therapy, 306,307
copper / zinc superoxide dismutase mutations,
aggregation, 306 copper binding, 284 folding variants, 284, 306 gain-of-function mutants,
304,305 neurodegeneration
mechanisms, 284-288, 306
overview, 270 types, 283
glutamate transporter loss, 304 incidence, 304 sporadic vs familial disease,
282,304 Angiogenesis,
cancer growth dependence, 455,456
590
copper role, 24, 456 tetrathiomolybdate inhibition,
cancer clinical trials, 457 diseases of
neovascularization, 458 preclinical studies, 456, 457
Aquatic organisms, cell signaling effects of copper,
calcium homeostasis, 424-426 tyrosine kinase cascade, 424
cellular mechanisms of copper homeostasis, 418
copper effects on cell compartments,
endoplasmic reticulum, 420,421
lysosomes,422,423 mitochondria, 421,422 plasma membrane,419,420
genotoxicity of copper,423 neurone effects of copper, 426
Arabidopsis thaliana, copper,
content, 543 essentiality, 543, 544 homeostasis networks,
CCH chaperone, 552-554 chelation systems, 545,546 endomembrane
transporters, 550, 552 plasma membrane
transporters, 546, 548-550
oxidative stress induction and defenses, 544, 545
transport and distribution proteins,
chaperone proteins, 488, 489 COPTl, 486, 487
Index
CPx transporters, 488 RANI, 487, 488
iron metabolism, copper role, 491 copper-independent
acquisition, 489 storage, 490
metal tolerance, 543 Ascorbate oxidase, Streptomyces,
517,519 ATOXl, see HAHI/ ATOXI ATP, copper uptake energetics,
195 ATP7 A, see MNK ATP7B, see PINA; WND Atxl,
Arabidopsis homolog, see CCH, Ccc2 interactions, 574 Chlamydomonas reinhardtii, 494 copper chaperone, 253,254,265
Azurin, water-protein interaction analysis, 98
B
Bag-I, Hsp70 interactions, 358 Bag-3, see Bis Bile, copper excretion, 16, 17 Bis,
CAIR-l clone, 365, 366 copper regulation of expression,
359,360 domains, 365 gene cloning, 359 phosphorylation, 365 sequence, 359 subcellular localization and
copper effects, 360, 361 synthesis and regulation in
HeLa cells, 361, 364
Index
tissue distribution, 359 bId mutants, see Streptomyces Blue copper proteins,
cupredoxins,
C
copper binding sites, 54 electron transfer processes,
56,57 spectroscopic characterization,
54 structures,54
overview of family, 54 plastocyanin electron transfer
process, see Plastocyanin sequence homology, 58-60 similarity analysis with respect
to molecular interaction properties,
descriptor classification, 67 molecular interaction field
similarity analysis, 67,68
overview, 61 protein interaction property
similarity analysis, 63, 65-67
sequence and structure analysis, 63
subfamily members and redox properties, 54, 55
CAB45584, Streptomyces, 519 CAB50963, Streptomyces, 519,
520 Caco-2 cell, see Intestine Cadherin, see E-cadherin Calcium, copper effects in aquatic
organism homeostasis, 424-426
591
Calcium ATPase, copper effects in aquatic
organisms, 419, 420, 424 P-type ATPase homology, 264
Cancer, angiogenesis, see Angiogenesis copper metabolism, 24, 25
Cartilage matrix glycoprotein (CMGP), copper binding and function, 21
Ccc2, Atx1 interactions, 574 Chlamydomonas reinhardtii, 494 copper,
loading of Fet3p, 241, 574 transport, 227
CCH, Atx1 homology, 552 C-domainfeatures, 552,553 expression and localization in
Arabidopsis, 553, 554 structure, 552
CCS, copper chaperone, 8, 190,253,
344,574 homology modeling, 92, 93 superoxide dismutase copper
delivery, 574, 575 Ceruloplasmin,
aceruloplasminemia, 25,190 acute phase reaction response,
20,24 apoceruloplasminemia,20 copper center types, 236, 392 copper distribution to tissues,
11,12,14,15,21,484 ferroxidase mechanism, 162, 163 function and diseases, 18,348 iron uptake role, 196, 236, 344
592
structure, 20 Wilson's disease levels, 235
Childhood cirrhosis, see Indian childhood cirrhosis; NonIndian childhood cirrhosis
Chlamydomonas reinhardtii, copper, assimilation, 492 Crr1 as master regulator, 494 deficiency adaptation,
iron,
cytochrome-c6 role, 491, 492 gene targets, 492 hypoxic expression of
deficiency targets, 493,494
plastocyanin role, 491, 492
assimilation, 494 copper role in metabolism,
496,497 deficiency-induced genes,
494,496 transporters and metabolic
enzymes, 495,496 CMGP, see Cartilage matrix
glycoprotein Confocal microscopy, intestine
tight junction copper toxicity studies,
E-cadherin staining, 409 F-actin localization, 407-411 fixation, 406, 407 image acquisition and analysis,
408 cop operon,
copper regulation, 179 genes, 177
CopA, discovery, 527
Index
metal specificity, 528 purification and properties,
528,530 CopB,
discovery, 527 kinetic parameters, 530, 531 metal specificity, 530 purification and properties, 531
Copper-containing amine oxidase, function and Menkes disease expression profiling, 347
Copper-dependent ceramide hydroxylase, function and Menkes disease expression profiling, 349
Copper-dependent sulfhydryl oxidase, function and Menkes disease expression profiling, 349
Copper deficiency, Chlamydomonas reinhardtii
adaptation, cytochrome-c6 role, 491, 492 gene targets, 492 hypoxic expression of
deficiency targets, 493,494
plastocyanin role, 491, 492 developmental effects, 249 features, 3, 4 genetic diseases, see Menkes
disease; Occipital horn syndrome
pig model, 235 Copper proteins, see also specific
proteins, copper center types and
classification by prosthetic centers, 81,83-85, 153, 154
Index
molecular modeling, see Molecular modeling, copper proteins
types and functions, overview, 81,82
Copper toxicosis, see Toxicity, copper
Copper / zinc superoxide dismutase,
amyotrophic lateral sclerosis mutations,
aggregation, 306 copper binding, 284 folding variants, 284, 306 gain-of-function mutants,
304,305 neurodegeneration
mechanisms, 284-288, 306
overview, 270 types, 283
antioxidant efficiency, 283 copper,
binding and function, 17, 19, 305
detoxification in yeast, 577 homology modeling, 92, 93 molecular dynamics simulation,
crystal structure refinement, 94 mutant studies, 97, 98 spectra analysis, 96, 97
molecular modeling, 91 peroxidase activity, 305, 306 pro-oxidant activity, 284 reactions, 305 redox reactions, 283, 284
COPT1, Arabidopsis thaliana copper transport, 486, 487, 547,549
593
COPT2, Arabidopsis thaliana copper transport, 547, 550
CopY, copper transfer mechanism
from CopZ, 181-184 DNA binding, 179, 180,
531-533 domains, 179 metal-binding studies, 179, 180 purification and properties, 533 structure, 531
CopZ, CopA interactions, 181 copper-induced conformational
change, 537, 538 CopY as copper transfer target,
181-184 intracellular copper routing,
533,535 metal-binding studies, 178,
179,538,539 sequence homology with other
copper chaperones, 178, 538,539
structure, 533,535,537,540 Cox17,
copper chaperone, 190,253, 344,575
Schizosaccharomyces pombe homolog, 580
CPx transporters, Arabidopsis thaliana, 488
Crr1, copper regulation in Chlamydomonas reinhardtii, 494
Ctr proteins, copper uptake,
mammalian cells, 192, 194 regulation, 195, 196
594
yeast, Saccharomyces cerevisiae,
191,252,253,482, 572-575
Schizosaccharomyces pombe, 578-580
energetics of copper uptake, 195, 197
human protein, see hCTRl Mac1p regulation of gene
expression, 476 structures,
Ctrlp, 572, 573 Ctr3p, 572, 573 Ctr4, 578, 579 Ctr5,580
transcriptional regulation by Maclp,476,576,577
Cufl, copper sensing, 581 deletion phenotypes, 580, 581 opposing regulation of copper
and iron genes, 581, 582 Cupredoxins, see Blue copper
proteins; Plastocyanin Cytochrome c oxidase,
bovine heart enzyme, metal content and
crystallization effects, 132, 133
phospholipid content, 133 subunits, 133
copper binding and function, crystal structures of redox
active metal sites, 140, 141, 143
electron transfer mechanism, 137
overview, 17, 131
oxygen reduction, chemistry, 137, 138 mechanism, 143, 144 resonance Raman
Index
spectroscopy, 138, 140 proton transfer,
Fourier transform infrared spectroscopy studies of redox-coupled conformational change, 147, 149
paths, 144-146 proton pumping
mechanisms, 149, 150 redox-coupled
conforma tional change, 146, 147
redox-coupled transfer mechanisms, 146
transfer through peptide bonds, 147
redox titration experiments, 135, 137
spectral studies, 134, 135 Cox17 copper chaperone, 190,
253,344,575 crystallization, 132 function and Menkes disease
expression profiling, 347 function, 131 purification, 131, 132 Streptomyces, 516, 517
Cytochrome-c6, Chlamydomonas reinhardtii copper deficiency adaptation, 491, 492
D
Deficiency, copper, see Copper deficiency
Index
Diamine oxidase, active site modeling, 93
Dietary copper, absorption, 4-9, 189, 190,250,
254,257,388-390,484 contents in food and tissue, 3,
4,370,385 deficiency effects, 3, 4 preloading effects on copper
homeostasis, 390 Recommended Daily Allowance,
3,385 WIlson disease management, 454
Differential display, copper status effects on gene
expression, 352, 353 Menkes disease expression
profiling, fibroblasts, 352 preliminary results, 351
overview, 349, 351 DMTI/Nramp2,
copper, transport, 7 uptake in yeast, 192
function and diseases, 18 metal specificity, 7, 13
Dopamine j3-hydroxylase, function
E
and Menkes disease expression profiling, 345, 346
E-cadherin, intestine tight junction copper toxicity studies, 409
EIN2, Arabidopsis copper transport, 547, 548
Electron paramagnetic resonance (EPR), Fet3, 155, 157
595
Electron spin-echo envelope modulation (ESEEM),
Fet3 copper-binding site structure, 157-160
principles, 157 Embryogenesis, copper role, 22 Endoplasmic reticulum (ER),
copper effects in aquatic organisms, 420, 421
plant copper transporters, 550, 552
Enterococcus hirae, advantages in copper studies,
527 copper ATPases, see CopA;
CopB copper proteins, see cop
operon; CopY; CopZ EPR, see Electron paramagnetic
resonance ER, see Endoplasmic reticulum ESEEM, see Electron spin-echo
envelope modulation EXAFS, see Extended X-ray
absorption fine structure Excretion, copper, 5, 16, 17, 250,
254,257,386 Extended X-ray absorption fine
structure (EXAFS),
F
CopZ, 178, 179 Fet3 binuclear type-3 copper
binding site structure, 160-162
F-actin, intestine tight junction copper toxicity studies, 407-411
Factor V,
596
function and Menkes disease expression profiling, 348,349
homology modeling, 92 Factor VIII, function and Menkes
disease expression profiling, 348,349
Ferroxidases, see Ceruloplasmin; Fet3p; Hephaestin
Fet3p, copper center types, 153-156 copper loading,
assay, 243 Ccc2 role, 241 chloride role, 243, 244 vacuolar gene roles, 242, 243
crystallization, 169 electron spin-echo envelope
modulation, copperbinding site structure studies, 157-160
extended X-ray absorption fine structure, binuclear type-3 copper-binding site structure, 160-162
ferroxidase activity, assays, 169, 170,239 kinetic constants, 168, 169,
172,239 mechanism, 163-165, 167, 168 prospects for study, 172, 173 reduction potential and
substrate specificity, 171,172
stopped-flow, 169, 170 Ftr1p complex, 240, 241, 482, 483 homology modeling,
copper-binding sites, 156, 157 molecular modeling, 92
Index
identification, 238 iron transport model, 237, 238 iron uptake, 482, 483 mutagenesis studies of iron
transport, 239, 240 oxygen consumption, 238, 239 recombinant protein expression
systems, insect cells, 167, 168 yeast, 168, 169
trafficking, 241 Fet4, metal specificity, 241 Force field, molecular dynamics
simulation, 90, 91 Fourier transform infrared
spectroscopy (FTIR), studies of redox-coupled conformational change in cytochrome c oxidase, 147, 149
Fox1, Chlamydomonas reinhardtii, 494
Fre proteins, copper reduction prior to yeast
uptake, 195 iron regulation of expression, 196 transcriptional regulation by
Mac1p, 576, 577 FTIR, see Fourier transform
infrared spectroscopy Ftr1p, Fet3p complex, 240, 241,
482,483 Fulminant hepatitis, see Long
Evans Cinnamon rat,
G
Gestation, copper metabolism, 23 Glutathione,
copper chaperone, 8, 9,190, 279,418
Index
H
intestinal epithelial copper handling, 389
liver copper handling, 391
HAH1/ ATOX1, copper chaperone, 7, 8, 190,
254,265,266 function and diseases, 18 knockout mouse phenotype, 9
hCTR1, chaperones for copper delivery, 8 copper transport, 6, 7,231,
232,254 domains, 253 function and diseases, 18 release of copper, 15 structure, 6
Heat shock proteins (HSPs), classes, 358 regulation of expression, 358
Hephaestin, function and diseases, 18,21,348
Histidine, copper binding in proteins, 9 copper transport, 9,12
HSPs, see Heat shock proteins
I
ICC, see Indian childhood cirrhosis Indian childhood cirrhosis (ICC),
animal models, 260, 261 causes, 260 geographic distribution, 370 heredity, 260
Infection, copper metabolism, 24 Inflammation, copper
metabolism, 24 Intestine,
597
chronic copper toxicity effects, 388-390
copper absorption, 4-9, 189, 190,250,254,257, 388-390,484
tight junction copper toxicity, Caco-2 cell model,
culture, 398 differentiation and
establishment of tight junctions, 401, 402
overview, 397, 398 clinical significance, 413, 414 copper complexes and
treatment, 402, 403 fluorescence labeling of
proteins and confocal microscopy,
Iron,
E-cadherin staining, 409 F-actin localization, 407-411 fixation, 406, 407 image acquisition and
analysis, 408 oxidative stress role, 411, 413 permeability to extracellular
markers, 400, 401 protein kinase C role, 413 reversibility of toxicity,
404,406 transepithelial electrical
resistance, 399, 400, 403, 404,406
transmission electron microscopy of ultrastructural changes, 411
absorption, 485 Alzheimer's disease role, 310, 311
598
anemia and copper protein defects, 571
Arabidopsis thaliana metabolism, copper role, 491 copper-independent
acquisition, 489 storage, 490
ceruloplasmin role in uptake, 196,236
Chlamydomonas reinhardtii metabolism,
assimilation, 494 copper role in metabolism,
496,497 deficiency-induced genes,
494,496 transporters and metabolic
enzymes, 495, 496 copper role in mammal
metabolism, 485, 486 distribution, storage, and
regulation in mammals, 485 Parkinson's disease role, 299,
300 yeast metabolism,
copper role in uptake, 196, 240,241,483
distribution, storage, and regulation, 482
Saccharomyces cerevisiae, 236, 237,482,483
Schizosaccharomyces pombe metabolism,
Cufl opposing regulation of copper and iron genes, 581, 582
uptake, 578 IRT1, Arabidopsis copper
transport, 547, 548
Index
L
Laccase, Streptomyces, 517, 519 Lactation, copper metabolism,
23,24 LEC rat, see Long-Evans
Cinnamon rat Lipid peroxidation, copper effects
on cell compartments in aquatic organisms, 419
Liver, chronic copper toxicity effects,
390-392 copper metabolism,
excretion, 16, 17, 257 uptake and transport, 13, 14,
257,391,392 Long-Evans Cinnamon (LEC) rat,
fulminant hepatitis and copper-metallothionein polymers,
Kupffer cell accumulation, 468,469
liver disease onset, 461, 462 penicillamine prevention,
461-463,469,470 subcellular sites of
hepatotoxicity, 465-468 ultrastructure analysis,
462,463 Wilson disease model, 228,
229,260,261,461 LOX, see Lysyl oxidase Lysosome,
copper detoxification, 465-468 copper effects in aquatic
organisms, 422, 423 Lysyloxidase (LOX),
copper binding and function, 21,346,347
Index
Menkes disease expression profiling, 346, 347, 352
M
Mac1p, copper detoxification, 476 CTR transcription regulation,
476,576,577 gene targets, 482 phosphorylation, 478 sensing of copper, 476, 477 thermodynamic model of
copper uptake vs detoxification, 477, 478
a2-Macroglobulin, copper binding, 11
Manganese, Parkinson's disease role, 299, 300
Marine organisms, see Aquatic organisms
Melatonin, circadian rhythm, 201, 203 PINA regulation, 205 regulation, 201, 202, 205, 206 synthesis, 201
Menkes disease, clinical features, 25, 35, 257,
258,323,324 copper protein functions and
expression profiling, ceruplasmin,348 copper-containing amine
oxidase, 347 copper-dependent ceramide
hydroxylase, 349 copper-dependent sulfhydryl
oxidase, 349 cytochrome-c oxidase, 347 differential display,
599
copper status effects on gene expression, 352,353
fibroblasts, 352 overview, 349, 351
dopamine b-hydroxylase, 345,346
factor V, 348, 349 factor VIII, 348, 349 hephaestin, 348 lysyl oxidase, 346, 347, 352 peptidyl a-amidating
monooxygenase,346 prospects for study, 353 superoxide dismutase, 347,
348 tyrosinase, 349
copper transport defects, 209, 240,251
diagnosis, 191,258,328 gene defect, see MNK incidence, 209 intracellular copper transport,
345 laboratory findings, 325, 326 mild disease, 257, 319, 325 molecular basis for variable
clinical phenotypes, 268, 269 mouse models, 259, 260, 281 neurological abnormalities, 281 pathophysiology, 322, 323 treatment, 258, 259, 328-330
MEP, see Molecular electrostatic potential
Metallothioneins, copper-metallothionein
complex, abundance in Wilson disease,
434,435
600
bUndUng, 5, 8, 19,20, 190,418 copper removal by
tetrathiomolybdate, see Tetrathiomolybdate
detoxification Un yeast, 577 Long-Evans Cinnamon rat,
hihnWnanthepatitis,and copper-metallothioneUn polymers,
Kupffer cell accumulation, 468,469
liver disease onset, 461, 462 penicillamUne prevention,
461--463,469,470 subcellular sites of
hepatotoxicity, 465--468
ultrastructure analysis, 462,463
preparation of complexes, 437
pro-oxidant activity, 434 functions, 19, 20, 358 Untestinal epithelial copper
handlUng, 389 liver copper handlUng, 391 metal-responsive elements in
expression regulation, 358 molecular modeling of bUndUng
sites, 93 plants, 545, 546 types, 190,484
Methane monooxygenase, see Particulate methane monooxygenase; Soluble methane monooxygenase
Methanotrophs, applications, 559 methane oxidation pathway, 560
particulate methane monooxygenase, see Particulate methane monooxygenase
soluble methane monooxygenase, see Soluble methane monooxygenase
types and genera, 559
Index
MIF, see Molecular Unteraction field Mitochondria, copper effects Un
aquatic organisms, 421, 422 MNK,
copper, bUndUng sites, 265 transport, 7, 8, 189 uptake regulation, 254, 257
developmental expression, 22 function and diseases, 18 gene,
alternative promoter evidence and characterization, 337-339
clonUng,211 locus, 319 promoter characterization,
336,337 regulation of expression, 336 structure, 209, 210, 261, 319
genotype-phenotype correlation, 321,322
gestation role, 23 lactation role, 24 molecular basis for variable
clinical phenotypes, 268, 269 mottled mouse mutants, 268,
269,319 mutations Un Menkes disease,
25,280,320,321
Index
P-type ATPase family, calcium ATPase homology,
264 cation recognition, 39 copper transport characteris
tics, 38, 39 homology with other
members, 36, 37, 262, 263 physiological roles, 37, 38 structural differences be
tween P1- and P2-ATPases, 39, 40
release of copper, 15, 16 splice variants,
ATP7A2-16, 334, 335 detection, 334 NML45, 335, 336 overview, 261, 262, 268,
333,334 structure, 37, 38, 262-266 tissue distribution, 15, 190,262,
364 trafficking,
CD8 reporter fusions, 214 copper-induced trafficking,
267,268 deletion mutant studies,
211-213 intracellular localization, 211 plasma membrane internaliza
tion signal identification, 218-220,222,223
steps, 223, 225 trans-Golgi network retention
signal identification, 214, 216, 267, 268
Molecular electrostatic potential (MEP), plastocyanin analysis, 76,78
601
Molecular interaction field (MIF), cupredoxin similarity analysis, 67, 68
Molecular modeling, copper
N
proteins, active site building, 93 availability, 99 building and modifying
structures, 86 comparative protein modeling,
building of model, 87, 88 overview, 86, 87 preliminary procedure, 87 refinement and model
quality, 88 computational chemistry, 86 definition, 85 dynamics simulation,
applications, crystal structure refinement,
94,95 interpretation of spectra,
95-98 protein-water interaction
analysis, 98 force field, 90, 91 overview, 88, 89 physics, 89, 90 potential function, 89
homology modeling, 92, 93 molecular graphics, 86 molecular mechanics, 86 mutant studies, 91, 92
Neurone, copper effects in aquatic organisms, 426
NICC, see Non-Indian childhood cirrhosis
602
Nitric oxide (NO), apoptosis role in amyotrophic
lateral sclerosis neurodegeneration, 286-288
reactive nitrogen speces, 279 Nitrous oxide reductase, crystal
structure refinement with molecular dynamics, 94, 95
NML45, structure and function, 335,336
NO, see Nitric oxide Non-Indian childhood cirrhosis
(NICC), animal models, 378, 379 gene,
ATP7B exclusion as candidate gene, 375
complicating factors in mapping, 377, 378
genomic screening, 376, 377 identification, 369, 371, 372 identity by descent and gene
mapping, 372, 374 German population features,
370,371 pathogenesis, 371, 372 prospects for study, 379, 380 Tyrol, Austria population
features, 369-371 Nramp,
o
Arabidopsis copper transport, 547,548
Nramp2, see DMT1/Nramp2
Occipital hom syndrome (OHS), clinical features, 325 diagnosis, 328 epidemiology, 257
Index
gene mutations, 268, 320, 321 genotype-phenotype correlation,
321,322 laboratory findings, 326, 327 mouse models, 259, 260 pathophysiology, 322, 323 treatment, 330
OHS, see Occipital hom syndrome
p
PAM, see Peptidyl a-amidating monooxygenase
Parkinson's disease (PD), clinical features, 289, 290 copper in pathogenesis, 290,
299,300 familial disease, 298 Lewy bodies, 298, 300 oxidative stress role, 299 parkin deletions, 299 selegiline management, 300 susceptibility locus, 299 a-synuclein mutations, 298,
300 transition metals in pathogenesis,
299,300 Particulate methane
monooxygenase (pMMO), copper regulation of expression,
566,567 genes, 564,565 metal binding, 564 prospects for study, 567 species distribution, 564 structure, 565 substrate specificity, 564 subunits, 564
PD, see Parkinson's disease Penicillamine,
Index
hepatotoxicity prevention in Long-Evans Cinnamon rat 461-463,469,470
Wilson disease management, 449,451
Peptidyl a-amidating monooxygenase (PAM), function and Menkes disease expression profiling, 346
Phytochelatin, plant synthases, 546 PINA,
circadian rhythm, 203 copper binding, 204, 206 melatonin synthesis role, 205 structure, 203,204 tissue distribution, 203 Wilson's disease studies, 206,
207 PIPSA, see Protein interaction
property similarity analysis PKC, see Protein kinase C Plant copper homeostasis, see
Arabidopsis thaliana Plasma membrane,
copper effects in aquatic organisms,419,420
plant copper transporters, 546, 548-550
Plastocyanin, see also Blue copper proteins,
Chlamydomonas reinhardtii copper deficiency adaptation, 491, 492
electron transfer process, quantitative analysis of thermodynamic and kinetic properties,
advantages over qualitative approaches, 79
603
cytochrome-f interactions, 69 mutant studies, 70 QSAR analysis of structural
determinants of cytochrome-f association,
descriptors, 76 molecular electrostatic
potential analysis, 76,78
overview, 75, 76 QSPR analysis,
descriptors, 71, 72 models, 72, 74, 75 overview, 71
function, 68, 69 molecular dynamics simulation,
crystal structure refinement, 94,95
water-protein interaction analysis, 98
molecular modeling, 91, 92 structure, 69, 70
pMMO, see Particulate methane monooxygenase
Prion protein (PrP), amyloidosis, 302 copper binding and function,
affinity, 105, 118 binding site, 290, 291, 302 carrier models, 109, 110, 120 copper transport, 303, 304 effects on biochemical prop-
erties and structure, 105, 106,303
overview, 21, 22, 25, 26, 270 peptide binding studies, 118,
119,302 prion disease roles, 109, 111,
123,124,126,302,303
604
protein endocytosis induction by copper, 107-110
regulation of copper release at synapse, 108
copper levels in prion disease brain, 126
disease types, 103, 104, 115, 270,301
doppel homology, 116, 117 function of normal protein,
overview, 104, 291, 301, 302 oxidative stress protection,
108,109,111,120,121,123 superoxide dismutase
activity, 106, 121, 123, 291,303
synaptic activity, 117, 118 infectivity, 115, 123, 124 knockout mice, 116-119 pathogenic form conversion,
103,123,290,301 structure, 104, 116 tissue distribution, 117 transmembrane forms, 301
Protein interaction property similarity analysis (PIPSA), cupredoxins, 63, 65-67
Protein kinase C (PKC), intestine tight junction copper toxicity role, 413
PrP, see Prion protein P-type ATPases, see also MNK;
WND, calcium ATPase homology, 264 cation recognition, 39 copper transport characteristics,
38,39 homology wth other members,
36,37,262,263
Q
Index
physiological roles, 37, 38 Streptomyces, 520-522 structural differences between
Pl- and P2-ATPases, 39,40
QSAR, see Quantitative structureactivity relationships
QSPR, see Plastocyanin Quantitative structure-activity
relationships (QSAR), peptides and proteins, 53 plastocyanin analysis of struc
tural determinants of
R
cytochrome-f association, descriptors, 76 molecular electrostatic
potential analysis, 76, 78 overview, 75, 76
ram cluster, Streptomyces, 511-513 RANI, Arabidopsis thaliana
copper transport, 487, 488, 550,552
RDA, see Recommended Daily Allowance
Reactive oxygen species (ROS), antioxidant defenses, 278 copper oxidation, 417, 418 copper role in generation, 81,
277,278,419 intestine tight junction copper
toxicity role, 411, 413 Parkinson's disease role, 290 plant cellular damage, 544
Recommended Daily Allowance (RDA), copper, 3, 385
Index
Resonance Raman spectroscopy, cytochrome c oxidase oxygen reduction mechanisms, 138,140
ROS, see Reactive oxygen species Rusticyanin, active site modeling,
93
s Saccharomyces cerevisiae,
copper, acquisition,
chaperones,574,575 high-affinity transport,
572-574 low-affinity uptake, 575, 576 transcriptional regulation of
transporters, 576, 577 detoxification, 577 proteins, see specific proteins
iron uptake, copper role, 196,240,241,483 overview, 236, 237, 482, 483
Schizosaccharomyces pombe, advantages in genetic analysis,
577,578 copper transporters, 578-580 Cufl,
copper sensing, 581 deletion phenotypes, 580, 581 opposing regulation of
copper and iron genes, 581,582
iron uptake, 578 Selegiline, Parkinson's disease
management,300 Smf proteins, copper uptake in
yeast, 575, 576 sMMO, see Soluble methane
605
monooxygenase SOD, see Superoxide dismutase Soluble methane monooxygenase
(sMMO), components and subunits,
560,561 copper regulation of expression,
565,566 genes, 561, 562 prospects for study, 567 recombinant protein expression
and copper effects, 563,564
sequence conservation between species, 562
species distribution, 560 structure, 561 substrate specificity, 560
Streptomyces, copper effects on differentiation,
aerial hyphae induction, 508,509
am! cluster role, 515 ram cluster role, 511-513 reproductive growth, 508, 509 strain differences, 510, 511
developmental mutants, bId mutants, 505, 506, 509, 510 whi mutants, 506, 507
genome analysis of copper proteins,
ascorbate oxidase, 517, 519 CAB45584,519 CAB50963,519,520 cytochrome-c oxidase, 516, 517 laccase, 517, 519 overview, 515, 516 P-type ATPases, 520-522 tyrosinase, 519
606
life cycle, 503, 505 signaling in development,
507,508 Superoxide dismutase (SOD), see
also Copper/zinc superoxide dismutase,
function and Menkes disease expression profiling, 347,348
prion protein activity, 106, 121, 123,291,303
types, 347, 348 a-Synuclein, Parkinson's disease
mutations, 298, 300
T
TEER, see Transepithelial electrical resistance
TEM, see Transmission electron microscopy
Tetrathiomolybdate (TTM), angiogenesis inhibition,
cancer clinical trials, 457 diseases of
neovascularization, 458 preclinical studies, 456, 457
clinical applications, 433, 436, 443 copper-metallothionein copper
removal, analysis, 437 selectivity, 439, 440 tetrathiomolybdate-complex
types, 437-439 mouse studies,
intraperitoneal injection, 439 intravenous injection, 439 selectivity of copper
removal, 439, 440 side effects, 440
Index
preparation, 436,437 Wilson disease management,
449,453 Toxicity, copper,
acceptable range of oral intake, 386
acute toxicity, 387, 388 aquatic organisms, see Aquatic
organisms chronic toxicity,
copper intake thresholds, 392,393
intestine, 388-390 liver, 390-392 defenses, 26 genetic diseases, see Indian
childhood cirrhosis; Non-Indian childhood cirrhosis; Wilson disease
idiopathic copper toxicosis, 370,379,380
intake sources, 370 intestinal tight junction toxicity,
Caco-2 cell model, culture, 398 differentiation and
establishment of tight junctions, 401, 402
overview, 397, 398 clinical significance, 413, 414
copper complexes and treatment, 402, 403
fluorescence labeling of proteins and confocal microscopy,
E-cadherin staining, 409 F-actin localization,
407-411 fixation, 406, 407
Index
image acquisition and analysis, 408
oxidative stress role, 411, 413 permeability to extracellular
markers, 400, 401 protein kinase C role, 413 reversibility of toxicity,
404,406 transepithelial electrical
resistance, 399, 400, 403, 404,406
transmission electron microscopy of ultrastructural changes, 411
mechanisms, 357, 370 neurotoxicity, 124 oxidative stress, 81 plants, 544, 545 species susceptibility, 26 yeast detoxification, 577
Transcuprein, copper binding, 9, 11 Transepithelial electrical resistance
(TEER), intestine tight junction copper toxicity, 399, 400,403,404,406
Transmission electron microscopy (TEM), intestine tight junction copper toxicity studies, 411
Trientine, Wilson disease management 448,449,451,453
TTM, see Tetrathiomolybdate Tyrosinase,
function and Menkes disease expression profiling, 349
Streptomyces, 519 Tyrosine kinase, copper effects in
aquatic organisms, 424
607
w whi mutants, see Streptomyces Wilson disease,
animal models, 260, 261 clinical features, 25, 206, 228,
260,269,282,444 copper in pathogenesis, 206,
250,260 diagnosis, 282, 444, 446, 448 frequency, 228, 443 gene defect, see WND liver biopsy, 448 Long-Evans Cinnamon rat
model, 228, 229, 260, 261, 461 molecular basis for variable
clinical phenotypes, 269 neurological degeneration, 282 prognosis,
compliance, 454, 455 recovery, 454 risk factors, 455
screening, 446, 448 treatment,
diet, 454 initial therapy, 452, 453 maintenance therapy, 451, 452 overview, 260, 282, 436 pediatric therapy, 453 penicillamine, 449, 451 pregnancy, 453 presymptomatic therapy, 453 tetrathiomolybdate therapy,
see Tetrathiomolybdate trientine, 448, 449, 451, 453 water treatment, 454 zinc, 448,451,453
WND, ATP-binding domain,
608
nucleotide-binding properties, 41-43
recombinant domain studies, ATP binding, 48, 49 purification, 48
copper transport, 7, 8, 189, 231-233,434,435
developmental expression, 22 domains, 230 function and diseases, 18,231,
434,435,484 gene structure, 229, 262 gestation role, 23 lactation role, 24 MNK homology, 229 mutations in WIlson disease, 444 N-terminal domain,
copper-binding properties, 40,41
copper-dependent domaindomain interactions and regulatory role, 4, 3-45
recombinant domain studies, copper loading and binding,
45,46 expression, 45 histidine tagging and
purification, 46-48 P-type ATPase family,
calcium ATPase homology, 264 cation recognition, 39 copper transport
characteristics, 38, 39 homology wth other
members, 36,37,262, 263 physiological roles, 37, 38 structural differences
between P1- and P2-ATPases, 39, 40
X
Index
PINA splice variant, see PINA release of copper, 16 splice variants, 262, 269 structure, 37, 38, 262-266 subcellular distribution, 190, 191 tissue distribution, 190,262,
365 trafficking,
copper-induced trafficking, 267 intracellular localization,
230,231 steps, 266, 267 trans-Golgi network retention,
266,267
X-ray crystallography, cytochrome c oxidase,
crystallization, 132
z
crystal structures of redoxactive metal sites, 140, 141,143
metal content, crystallization effects, 132, 133
Fet3 crystallization, 169 multicopper oxidase structures,
156,157 structure refinement with
molecular dynamics simulation, 94, 95
Zinc, Alzheimer's disease role, 310, 311 Parkinson's disease role, 299, 300 Wilson disease management,
448,451,453 ZIP, Arabidopsis copper transport,
547,548