Download
1 / 1
10 likes | 169 Views
Ligand search and data mining of Structural Genomics structures. Abhinav Kumar, Herbert Axelrod, Ashley Deacon Structure Determination Core, Joint Center for Structural Genomics (JCSG), Stanford Synchrotron Radiation Laboratory, Menlo Park, CA, USA. 11. 10. 2. 1. 6. 3. 4. 5. 9. 8.
E N D
Ligand search and data mining of Structural Genomics structures Abhinav Kumar, Herbert Axelrod, Ashley Deacon Structure Determination Core, Joint Center for Structural Genomics (JCSG), Stanford Synchrotron Radiation Laboratory, Menlo Park, CA, USA 11 10 2 1 6 3 4 5 9 8 The Role of the Structure Determination Core in the JCSG The JCSG Target Pipeline • Screen Crystals and Collect Data • Automatically Process Data • Refine and Evaluate Structures • Disseminate Information* • Publish • Web based Tools • TOPSPAN (www.topsan.org) • Ligand Search (smb.slac.stanford.edu/public/jcsg/cgi/jcsg_ligand_check.pl) The Joint Center for Structural Genomics (JCSG) Autoindex Integrate Scale Solve Trace Summary of Ligands (1601 structures) Ligands (288 structures; 156 different ligands): UNL(70), UNX(22), NDP(7), MA7(6), SIN(6), LLP(6), NAG(5), UNK(4), PLM(4), APC(3), GUN(3), NCA(3), SUC(3), BAL(3), GLC(3), PAF(3), SRT(2), PDC(2), APR(2), GAL(2), CSD(2), NCN(2), SAI(2), BIO(2), CEI(2), GNP(2), HMH(2), SAP(2), BGC(2), G4P(2), TCL(2), MPO(2), SNN(2), ZID(2), 144(2), ANP(2), DGT(2), PCP(2), PAJ(2), NIO(1), ABF(1), IPR(1), MTA(1), CP(1), MLT(1), DI6(1), MED(1), HE7(1), MLZ(1), 5GP(1), MTO(1), CDP(1), I3A(1), 665(1), 2PL(1), CE1(1), HED(1), G1P(1), CSY(1), FRU(1), PLG(1), THF(1), B1M(1), ACP(1), DU(1), MMZ(1), OHA(1), 16A(1), 744(1), THT(1), M7P(1),3GC(1), CF5(1), PEO(1), PEP(1), CTZ(1), 5PP(1), ADE(1), FT6(1), KEG(1), LUM(1), XLS(1), BAM(1), ADN(1), PMP(1), ADQ(1), B33(1), 468(1), DGI(1), G3H(1), OXG(1), NDS(1), B75(1), SAL(1), P3S(1), STH(1), FEO(1), G3P(1), OXN(1), FES(1), TYD(1), 3SL(1), 8PP(1), CO2(1), 8PS(1), MP5(1), NTM(1), PNS(1), AES(1), SIB(1), UVW(1), TRE(1), APK(1), LDA(1), NAI(1), PYR(1), COH(1), NMN(1), MAN(1), BFD(1), HHP(1), RIP(1), RBF(1), ORO(1), TSA(1), AAT(1), DTP(1), DON(1), DEP(1), UPG(1), HXA(1), NPO(1), DTY(1), CRO(1), TNE(1), C2E(1), BDF(1), AGC(1), PHT(1), OSB(1), NVA(1), NIG(1), BDN(1), PRP(1), SOG(1), PB(1), 566(1), AGS(1), TLP(1), 1PS(1), DUT(1), CXS(1), GTP(1), GEQ(1), G6P(1), 641(1) Co-factors (222 structures; 21 different co-factors): NAD(40), FMN(35), COA(18), NAP(17), ADP(16), PLP(15), FAD(15), SAM(14), ATP(9), SAH(9), AMP(9), HEM(8), ACO(7), GDP(4), FS4(3), U5P(2), MLC(1), COD(1), CNC(1), UTP(1), CTP(1) Metal Ions (643 structures; 30 different metal ions): MG(174), ZN(173), NA(101), CA(82), NI(38), MN(34), FE(26), K(16), FE2(9), CD(8), PT(8), HG(7), CO(5), SM(2), WO4(2), PR(2), AU(2), BA(1), CS(1), MW2(1), SE(1), ARS(1), ZN3(1), O4M(1), YT3(1), LI(1), MO2(1), MO3(1), VO4(1), MO6(1) Non-metal Ions (681 structures; 22 different non-metal ions): SO4(322), CL(236), PO4(115), NO3(11), IOD(10), BR(10), SCN(8), CO3(4), CAC(4), POP(3), AZI(3), SUL(2), BCT(2), ALF(2), OXL(2), PER(1), SO3(1), MLI(1), PO3(1), THJ(1), 1AL(1), NH4(1) Organics (87 structures; 27 different organics): IPA(13), EOH(12), BME(9), AKG(5), BEZ(5), TLA(5), SEO(5), TAR(4), ETX(4), DTT(4), PGO(2), OAA(2), DMS(2), ACE(2), IOH(1), MLA(1), DOX(1), XYL(1), DAO(1), 3OH(1), MOH(1), PPI(1), AZ1(1), FOR(1), MYR(1), GTT(1), LMT(1) Buffers (240 structures; 15 different buffers): ACT(87), ACY(47), FMT(36), CIT(27), TRS(16), EPE(15), MES(12), IMD(8), TMN(2), 10A(2), BTB(2), ICT(1), CPS(1), FLC(1), NHE(1) Precipitants (98 structures; 13 different precipitants): PEG(38), PG4(29), PGE(16), 1PE(8), P6G(7), PE4(3), P33(3), PE5(2), 2PE(2), PEF(1), BU3(1), 1PG(1), PE8(1) Salts (3 structures; 3 different salts): DPO(1), AF3(1), PPC(1) Detergents (2 structures; 1 different detergents): BOG(2) Cryos (491 structures; 5 different cryos): GOL(240), EDO(233), MPD(32), EGL(3), CRY(2) JCSG Ligand Search Each project moves from target selection through publication along the Target Pipeline. The JCSG (www.jcsg.org) is one of the four large-scale structural genomics centers funded by NIGMS as part of the production phase of the Protein Structure Initiative (PSI). More than 2600 structures have been deposited into the PDB by the PSI centers as of 2007, of which the JCSG has contributed over 500 structures. * in collaboration with BIC Unique PSI Ligands 7 Novel Folds in JCSG Structures Binding Modes FMN NAD PLP Search Results (35 hits) N Target PDB PFAM Accession Description Organism Ligands PSI 1 FB10607B 2r6v PF01613 NP_142786.1 Crystal Structure of FMN-binding Protein (NP_142786.1) from Pyrococcus Horikoshii at 1.35 Å resolution Pyrococcus Horikoshii Ot3 EDOFMNNCA JCSG 2 FH7614A 2ig6 PF01243 NP_349178.1 Crystal Structure of NIMC/NIMA Family Protein (NP_349178.1) from Clostridium Acetobutylicum at 1.80 Å resolution Clostridium Acetobutylicum EDOFMNSO4 UNL JCSG 3 FJ9446A 2ou5 PF01243 YP_508196.1 Crystal Structure of Pyridoxamine 5'-phosphate Oxidase- Related FMN-binding (YP_508196.1) From Jannaschia Sp. Ccs1 at 1.60 Å resolution Jannaschia Sp. Ccs1 FMNGOLSO4 JCSG . … … … … … … … … 2ICH 1VR0 1VJL 1KQ4 1VKY 34 SGT98480 1q45 PF00724 NP_178662.1 12-0xo-Phytodienoate Reductase Isoform 3 Arabidopsis Thaliana FMN CESG 35 TB0885A 1vp8 PF08981 NP_068944.1 Crystal Structure of Hypothetical Protein (NP_068944.1) from Archaeoglobus Fulgidus at 1.30 Å resolution Archaeoglobus Fulgidus Dsm 4304 FMN UNL JCSG 1VQ0 1VKM 1VK9 1VRM Ligand Visualization Links HIC-Up: ACYADPAMPBRCACLEDOFMNGLCGOLIODMGNCANIOROP33PO4SO4 Ligand Depot: ACYADPAMPBRCACLEDOFMNGLCGOLIODMGNCANIOROP33PO4SO4 GNF & TSRI (Crystallomics Core) Scott Lesley Mark Knuth Dennis Carlton Thomas Clayton Kevin D. Murphy Christina Trout Marc Deller Daniel McMullan Heath Klock Polat Abdubek Claire Acosta Linda M. Columbus Julie Feuerhelm Joanna C. Hale Thamara Janaratne Hope Johnson Linda Okach Edward Nigoghossian Sebastian Sudek Aprilfawn White Bernhard Geierstanger Glen Spraggon Ylva Elias Sanjay Agarwalla Charlene Cho Bi-Ying Yeh Anna Grzechnik Jessica Canseco Mimmi Brown UCSD & Burnham (Bioinformatics Core) John Wooley Adam Godzik Slawomir Grzechnik Lukasz Jaroszewski Dana Weekes Lian Duan Sri Krishna Subramanian Natasha Sefcovic Piotr Kozbial Andrew Morse Prasad Burra Tamara Astakhova Josie Alaoen Cindy Cook TSRI (NMR Core) Kurt Wüthrich Reto Horst Maggie Johnson Amaranth Chatterjee Michael Geralt Wojtek Augustyniak Pedro Serrano Bill Pedrini William Placzek Stanford /SSRL Structure Determination Core Keith Hodgson Ashley Deacon Mitchell Miller Debanu Das Hsiu-Ju (Jessica) Chiu Kevin Jin Christopher RifeQingping Xu Silvya Oommachen Scott Talafuse Henry van den Bedem Ronald Reyes Christine Trame Scientific Advisory Board Sir Tom Blundell Robert Stroud Univ. Cambridge Center for Structure of Membrane Proteins Homme Hellinga Membrane Protein Expression Center Duke University Medical CenterUC San Francisco James Naismith James Paulson The Scottish Structural Proteomics facilityConsortium for Functional Glycomics Univ. St. Andrews The Scripps Research Institute Soichi Wakatsuki Todd Yeates Photon Factory, KEK, Japan UCLA-DOE Inst. for Genomics and Proteomics James Wells UC San Francisco The JCSG is supported by the NIH Protein Structure Initiative (PSI) Grant U54 GM074898 from NIGMS (www.nigms.nih.gov). Unique Ligands 10-Oxohexadecanoic acid (OHA) bound to the structure of Ferredoxin-like Protein (JCVI_PEP_1096682647733) from an environmental metagenome (Unidentified Marine Microbe) (2OD6) (R)-2-Hydroxy-3-Sulfopropanoic acid (3SL) bound to the structure of putative 2-phosphosulfolactatetitle 2 phosphatase from Clostridium Acetobutylicum (1VR0) Indole-3-Carboxaldehyde (I3A) bound to the structure of tellurite resistance protein of cog3793 (zp_00109916.1) from Nostoc Punctiforme PCC 73102 (2OU3) FB8805A (2Q9K) Unknown protein Unknown Ligands (UNL) FK9436A (2OH1) Acetyltransferase Gnat family
