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 UCSD & Burnham (Bioinformatics Core) John Wooley Adam GodzikSlawomir Grzechnik Lukasz Jaroszewski Dana Weekes Lian Duan Sri Krishna Subramanian Natasha SefcovicPiotr 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 HodgsonAshley Deacon Mitchell Miller Debanu Das Hsiu-Ju (Jessica) ChiuKevin Jin Christopher RifeQingping Xu Silvya OommachenScott Talafuse Henry van den BedemRonald Reyes Christine Trame Scientific Advisory Board Sir Tom BlundellRobert Stroud Univ. Cambridge Center for Structure of Membrane Proteins Homme Hellinga Membrane Protein Expression Center Duke University Medical Center UC San Francisco James Naismith James Paulson The Scottish Structural Proteomics facility Consortium 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 GM from NIGMS ( GNF & TSRI (Crystallomics Core) Scott LesleyMark KnuthDennis Carlton Thomas ClaytonKevin D. MurphyChristina Trout Marc DellerDaniel McMullanHeath Klock Polat Abdubek Claire AcostaLinda M. Columbus Julie FeuerhelmJoanna C. HaleThamara Janaratne Hope JohnsonLinda Okach Edward Nigoghossian Sebastian SudekAprilfawn WhiteBernhard Geierstanger Glen SpraggonYlva Elias Sanjay Agarwalla Charlene ChoBi-Ying YehAnna Grzechnik Jessica CansecoMimmi Brown The JCSG ( 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. The Joint Center for Structural Genomics (JCSG) 1 Each project moves from target selection through publication along the Target Pipeline. The JCSG Target Pipeline 2 AutoindexIntegrateSolveTraceScale 1.Screen Crystals and Collect Data 2.Automatically Process Data 3.Refine and Evaluate Structures 4.Disseminate Information*  Publish  Web based Tools  TOPSPAN (  Ligand Search ( smb.slac.stanford.edu/public/jcsg/cgi/jcsg_ligand_check.pl) * in collaboration with BIC The Role of the Structure Determination Core in the JCSG 3 JCSG Ligand Search 4 5 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) 7 Search Results (35 hits) ACYACY ADP AMP BR CA CL EDO FMN GLC GOL IOD MG NCA NI ORO P33 PO4 SO4ADPAMPBRCACLEDOFMNGLCGOLIODMGNCANIOROP33PO4SO4Ligand Depot: ACYACY ADP AMP BR CA CL EDO FMN GLC GOL IOD MG NCA NI ORO P33 PO4 SO4ADPAMPBRCACLEDOFMNGLCGOLIODMGNCANIOROP33PO4SO4HIC-Up: Ligand Visualization Links JCSGFMN FMN UNL Archaeoglobus Fulgidus Dsm 4304 Crystal Structure of Hypothetical Protein (NP_ ) from Archaeoglobus Fulgidus at 1.30 Å resolution NP_ PF089811vp8TB0885A35 CESGFMNArabidopsis Thaliana 12-0xo-Phytodienoate Reductase Isoform 3NP_ PF007241q45SGT ……………………. JCSGFMN GOLFMN GOL SO4SO4 Jannaschia Sp. Ccs1 Crystal Structure of Pyridoxamine 5'- phosphate Oxidase- Related FMN-binding (YP_ ) From Jannaschia Sp. Ccs1 at 1.60 Å resolution YP_ PF012432ou5FJ9446A3 JCSGEDO FMNEDO FMN SO4 UNLSO4 Clostridium Acetobutylicum Crystal Structure of NIMC/NIMA Family Protein (NP_ ) from Clostridium Acetobutylicum at 1.80 Å resolution NP_ PF012432ig6FH7614A2 JCSGEDO FMN NCA Pyrococcus Horikoshii Ot3 Crystal Structure of FMN-binding Protein (NP_ ) from Pyrococcus Horikoshii at 1.35 Å resolution NP_ PF016132r6vFB10607B1 PSILigandsOrganismDescriptionAccessionPFAMPDBTargetN 6 Unique Ligands 9 (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_ ) from Nostoc Punctiforme PCC (2OU3) 10-Oxohexadecanoic acid (OHA) bound to the structure of Ferredoxin-like Protein (JCVI_PEP_ ) from an environmental metagenome (Unidentified Marine Microbe) (2OD6) FK9436A (2OH1) Acetyltransferase Gnat family FB8805A (2Q9K) Unknown protein Unique PSI Ligands 8 Unknown Ligands (UNL) Novel Folds in JCSG Structures 10 2ICH 1VQ0 1VR01VJL1KQ41VKY 1VRM1VK91VKM Binding Modes 11 FMNNADPLP