mining psi structures: jcsg ligand server

JCSG Annual Meeting 2008The Expanding Protein Universe

Mining PSI Structures:JCSG Ligand Server

Abhinav Kumar

Structure Determination Core


Outline

• Introduction and history• Examples of use (live)• Statistics• Unique ligands• Binding mode studies• Usage


Introduction and History

• Herb’s compilation of JCSG data– Porting Excel sheet to Web server

http://smb.slac.stanford.edu/public/jcsg/cgi/jcsg_ligand_check.pl

• Automating tasks– Andrew’s script to produce the list of PSI structures released by PDB – Script to download the pdbs and extract relevant information

» Database for the Ligand server


Examples of Use


Live

• Examples of query entry

• Executing search

• Explanation of links in the search results

• Summary


Number of Structures and unique Compounds

PSI: solid barJCSG: open bar

288158

9227

Distribution of Ligands


Ligands

67/74 (JCSG)18/22 (SECSG)


Co-factors 22 in PSI, 20 in JCSG

Organics 22 in PSI, 6 in JCSG


IonsMetal

24 in PSI,10 in JCSG

Non-metal 21 in PSI,12 in JCSG


Buffers (14,10) Precipitants (13,9)

Cryos


Cryo-protectant agents in JCSG Structures

Cryo# of times used

# of times observed in structure

EDO 230 179 (77.8 %)

GOL 213 93 (43.7 %)

MPD 66 23 (34.8 %)

PEG200 56 18 (32.0 %)

PEG400 35 10 (28.6 %)


PFAMs (1292 in PSI, 392 in JCSG)129659 10 9 4 7 5 10

1011 7 10 13 15 8 6 9 14 11

15 11 14 13 10 18 11 14 18

Number of ligands


PDB ID Ligand Name ID Center

1KPH, 1KPI Didecyl-Dimethyl-Ammonium 10A TBSGC

1X92 D-Glycero-D-Mannopyranose-7-Phosphate M7P MCSG

1LW4 3-Hydroxy-2-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl- Pyridin-4-Ylmethyl)-Amino]-Butyric Acid

TLP NYSGXRC

2B4B N-Ethyl-N-[3-(Propylamino)Propyl]Propane- 1,3-Diamine B33 NYSGXRC

1O8B Beta-D-Arabinofuranose-5'-Phosphate ABF MCSG

1RTW (4-Amino-2-Methylpyrimidin-5-Yl)Methyl Dihydrogen Phosphate MP5 NESG

1TUF Azelaic Acid AZ1 NYSGXRC

2PUZ N-(Iminomethyl)-L-Glutamic Acid NIG NYSGXRC

2OU3 1h-Indole-3-Carbaldehyde I3A JCSG

2OSU 6-Diazenyl-5-Oxo-L-Norleucine DON MCSG

1M33 3-Hydroxy-Propanoic Acid 3OH MCSG

2Q09 3-[(4s)-2,5-Dioxoimidazolidin-4-Yl]Propanoic Acid DI6 NYSGXRC

1N2H, 1N2I Pantoyl Adenylate PAJ TBSGC

2GVC 1-Methyl-1,3-Dihydro-2h-Imidazole-2-Thione MMZ NYSGXRC

1BVR Trans-2-Hexadecenoyl-(N-Acetyl-Cysteamine)- Thioester THT TBSGC

1Y80 Co-5-Methoxybenzimidazolylcobamide B1M SECSG

2A3L Coformycin 5'-Phosphate CF5 CESG

1VR0 (2r)-3-Sulfolactic Acid 3SL JCSG

2NW9 6-Fluoro-L-Tryptophan FT6 NESG

1Y0G 2-[(2e,6e,10e,14e,18e,22e,26e)-3,7,11,15,19,23,27,31- Octamethyldotriaconta-2,6,10,14,18,22,26,30- Octaenyl]Phenol

8PP NYSGXRC

1QPR 5-Phosphoribosyl-1-(Beta-Methylene) Pyrophosphate PPC TBSGC

1Z2L Allantoate Ion 1AL NYSGXRC

1XKL 2-Amino-4h-1,3-Benzoxathiin-4-Ol STH NESG

1P44 5-{[4-(9h-Fluoren-9-Yl)Piperazin-1-Yl]Carbonyl}- 1h-Indole GEQ TBSGC

2OD6 10-Oxohexadecanoic Acid OHA JCSG

Unique Ligands (25) in PSI Structures


Examples of Unique Ligands

(R)-2-Hydroxy-3-Sulfopropanoic acid (3SL) bound to the putative 2-phosphosulfolactatetitle 2 phosphatase from Clostridium Acetobutylicum (1VR0)

Indole-3-Carboxaldehyde (I3A) bound to tellurite resistance protein of COG3793 (ZP_00109916.1) from Nostoc Punctiforme PCC 73102 (2OU3)

10-Oxohexadecanoic acid (OHA) bound to Ferredoxin-like protein (JCVI_PEP_1096682647733) from an environmental metagenome (unidentified marine microbe) (2OD6)


Unknown Ligands (UNL)

FB8805A (2Q9K) Protein of unknown function FK9436A (2OH1) Acetyltransferase Gnat family


Binding Mode Studies

• FMN bound in over 340 structures in RCSB

• Binding mode variation in due to the torsional flexibility in the molecule

• Several ligands/co-factors bound to the proteins• Binding mode studies for co-factors

– FMN as an example


Unique binding modes observed in different PFAM families

PFAM PSI Non-PSI Total

PF01070FMN-dependent dehydrogenase

0 8 8

PF00881DHOdehase

9 8 17

PF00258Flavodoxin _1

3 13 16

PF00724Oxidored._FMN

2 8 10

PF01613Flavin reductase-like

2 7 9

PF01180Nitroreductase

1 8 9

PF01243Pyridox._oxidase

7 14 21


PF01070(FMN-dependent dehydrogenase )

PF00881(DHOdehase)

PF00724(Oxidored._FMN )

PF00258(Flavodoxin _1)


PF01613(Flavin reductase-like)

PF01180(Nitroreductase)

PF01243(Pyridox._oxidase)

1y30


PF01264

Two structures of Chorismate Synthase1qxo, 1um0


First Structures in PFAMs for Protein-Ligand complexes

Ligand PFAM (First PDB)

ACO PF01121(2F6R)

ADP PF01966(2Q14) PF01266(3C4N) PF02641(1O51) PF01637(2FNA) PF00437(1G6O) PF01812(1U3G) PF00265(1XX6) PF00154(1MO3)

AMP PF02569(2A7X) PF01687(1T6Y) PF00582(2GM3) PF02254(2G1U)

ATP PF02569(2A84) PF01513(1Z0S) PF03328(1U5V) PF06973(2PBZ) PF00582(1MJH)

COA PF02522(2NYG) PF02566(2ONF) PF02550(2OAS) PF02629(1Y81) PF02515(1Q6Y)

FAD PF00743(2GV8) PF04954(2GPJ) PF03486(2GQF) PF01243(2FG9)

FMN PF07972(1RLJ) PF08981(1T57) PF04289(2IML) PF03358(1NNI) PF01613(1EJE)

GDP PF01996(2PHN) PF03193(1U0L) PF01966(2HEK)

HEM PF04261(2IIZ) PF08933(2NWB)

NAD PF00571(2RC3) PF06408(2PH5) PF01933(2O2Z) PF01958(1J5P) PF01513(1Y3I) PF01467(1EJ2)

NAP PF09130(1I36) PF01262(2RIR) PF01408(1ZH8) PF00465(1O2D) PF01513(1Z0U) PF08501(1NVT)

PLP PF01168(1CT5)

SAH PF01795(1M6Y) PF04445(2OYR) PF02353(1KPG)

SAM PF04672(2QE6) PF00590(2NPN) PF01980(2NV4) PF03054(2HMA) PF04013(2QMM) PF02384(2F8L) PF01795(1N2X) PF01555(1G60) PF08241(1P91)


Page Visits (36 different domains)

Tracking since September 2007


UCSD & BurnhamBioinformatics Core

John WooleyAdam Godzik

Lukasz JaroszewskiSlawomir Grzechnik

Sri Krishna SubramanianAndrew Morse

Tamara AstakhovaLian Duan

Piotr KozbialDana Weekes

Natasha SefcovicPrasad Burra

Konstantina BakolitsaAndrei Istomin

Kyle EllrottJosie AlaoenCindy Cook

GNF & TSRICrystallomics Core

Scott LesleyMark KnuthHeath Klock

Dennis CarltonThomas Clayton

Marc DellerDaniel McMullan Polat Abdubek Julie FeuerhelmJoanna C. Hale

Thamara JanaratneHope Johnson

Edward NigoghossianLinda Okach

Sebastian SudekGlen Spraggon

Bernhard GeierstangerSanjay AgarwallaAnna Grzechnik

Connie ChenDustin Ernst

Regina GorskiSachin Kale

Amanda NopakunChristina PuckettTiffany Wooten

Jessica CansecoMimmi Brown

Scientific Advisory BoardSir Tom BlundellUniv. CambridgeHomme Hellinga

Duke University Medical CenterJames Naismith

The Scottish Structural Proteomics Facility Univ. St. AndrewsJames Paulson

Consortium for Functional Glycomics,The Scripps Research Institute

Robert StroudCenter for Structure of Membrane Proteins,

Membrane Protein Expression Center, UCSF Soichi Wakatsuki

Photon Factory, KEK, JapanJames Wells

UC San FranciscoTodd Yeates

UCLA-DOE, Inst. for Genomics and Proteomics

TSRI, NMR CoreKurt Wüthrich

Reto Horst Maggie Johnson

Amaranth ChatterjeeMichael Geralt

Wojtek AugustyniakPedro Serrano

Bill PedriniBiswaranjan Mohanty

Jin-Kyu Rhee

TSRI Administrative Core

Ian WilsonMarc ElsligerGye Won Han

David MarcianoHenry Tien

Lisa van Veen

Stanford /SSRL Structure Determination Core

Keith HodgsonAshley DeaconMitchell Miller

Herbert AxelrodHsiu-Ju (Jessica) Chiu

Kevin JinChristopher Rife

Qingping XuSilvya Oommachen

Henry van den BedemScott TalafuseRonald Reyes

Abhinav KumarChristine Trame

Debanu DasWinnie Lam

The JCSG is supported by the NIGMS Protein Structure Initiative Grant U54 GM074898

Ex officio founding members JCSG-1Raymond Stevens , TSRI

Susan Taylor, UCSD Peter Kuhn, SSRL/TSRI

Duncan McRee, TSRI/SyrrxPeter Schultz, TSRI/GNF


Acknowledgements

Herb, Andrew, Ashley


JCSG Annual Meeting 2007

mining psi structures: jcsg ligand server

Documents