1. 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
Ligand Search and Data Mining of
Structural Genomics Structures
UCSD & Burnham
(Bioinformatics Core)
John Wooley Adam Godzik
Lukasz Jaroszewski Slawomir Grzechnik
Lian Duan Sri Krishna Subramanian
Natasha Sefcovic Piotr Kozbial
Andrew Morse Prasad Burra
Tamara Astakhova Josie Alaoen
Cindy Cook Dana Weekes
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 Rife Qingping 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 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 ( Portions of this research were carried out at the Stanford Synchrotron Radiation Laboratory (SSRL). The SSRL is a national user facility operated by Stanford University on behalf of the U.S. Department of Energy, Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program is supported by the Department of Energy, Office of Biological and Environmental Research, and by the NIH.
GNF & TSRI
(Crystallomics Core)
Scott Lesley Mark Knuth Heath Klock
Dennis Carlton Thomas Clayton Kevin D. Murphy
Marc Deller Daniel McMullan Christina Trout
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
(Admin Core)
Ian Wilson
Marc Elsliger
Gye Won Han
David Marciano
Henry Tien
Xiaoping Dai
Lisa van Veen
Annual meeting with SAB 2007
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 well over 500 structures. Although the major part of JCSG's resources is dedicated to protein structure determination, we are also making efforts to disseminate information gained from these structures to a larger community of researchers. Here we report the development of a web-based data mining engine (smb.slac.stanford.edu/public/jcsg/cgi/jcsg_ligand_check.pl) that queries all of the PSI structures based on a variety of search criteria. The main objective is to extract ligands, biological or otherwise, bound to these structures, and to explore them further with a number of associated links. In addition, the structures can be queried by a host of other criteria, such as target names, PDB IDs, PFAM family names, structure descriptions, organisms, and PSI centers. Preliminary analysis indicates that 1515 of these PSI structures have some type of bound ligand, metal or solvent molecules, and 262 contain 136 unique biological ligands. Interestingly, several of these ligands had not been previously identified in structures in the PDB. In addition, 21 different co-factors have been observed in 210 structures.
The Joint Center for Structural Genomics (JCSG) 1 5
Search Results (35 hits)
ACY ADP AMP BR CA CL EDO FMN GLC GOL IOD MG NCA NI ORO P33 PO4 SO4
Ligand Depot:
HIC-Up:
Ligand Visualization Links
JCSG
FMN UNL
Archaeoglobus Fulgidus Dsm 4304
Crystal Structure of Hypothetical Protein (NP_ ) from Archaeoglobus Fulgidus at 1.30 Å resolution
NP_
PF08981
1vp8
TB0885A 35
CESG
FMN
Arabidopsis Thaliana
12-0xo-Phytodienoate Reductase Isoform 3
NP_
PF00724
1q45
SGT98480 34 … .
FMN GOL SO4
Jannaschia Sp. Ccs1
Crystal Structure of Pyridoxamine 5'-phosphate Oxidase- Related FMN-binding (YP_ ) From Jannaschia Sp. Ccs1 at 1.60 Å resolution
YP_
PF01243
2ou5
FJ9446A 3
EDO FMN SO4 UNL
Clostridium Acetobutylicum
Crystal Structure of NIMC/NIMA Family Protein (NP_ ) from Clostridium Acetobutylicum at 1.80 Å resolution
NP_
2ig6
FH7614A 2
EDO FMN NCA
Pyrococcus Horikoshii Ot3
Crystal Structure of FMN-binding Protein (NP_ ) from Pyrococcus Horikoshii at 1.35 Å resolution
NP_
PF01613
2r6v
FB10607B
PSI
Ligands
Organism
Description
Accession
PFAM
PDB
Target N
A Typical Search Result 4
Examples of Search Queries
Unique PSI Ligands 8
Autoindex
Integrate
Solve
Trace
Scale
Screen Crystals and Collect Data
Automatically Process Data
Refine and Evaluate Structures
Disseminate Information*
Publish
Web based Tools
TOPSPAN (
Ligand Search (smb.slac.stanford.edu/public/jcsg/cgi/jcsg_ligand_check.pl)
* in collaboration with JCSG Bioinformatics Core
The Role of the Structure Determination Core in the JCSG 6
Ligands bound to JCSG Structures with New Folds 10
2ICH
1VQ0
1VR0
1VJL
1KQ4
1VKY
1VRM
1VK9
1VKM
9 out of 26 new fold structures from JCSG have bound ligands, which identify their active sites and give some clues to function. Often the ligands are modeled as UNL, because their precise identity is unknown.
JCSG Ligand Search
Unique Ligands 9
(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_ ) from Nostoc Punctiforme PCC (2OU3)
10-Oxohexadecanoic acid (OHA) bound to Ferredoxin-like protein (JCVI_PEP_ ) from an environmental metagenome (unidentified marine microbe) (2OD6)
FK9436A (2OH1)
Acetyltransferase Gnat family
FB8805A (2Q9K)
Protein of unknown
function
Unknown Ligands (UNL)
Distribution of Ligands 7
Co-factors
Metal Ions
Non-metal Ions
Buffers
Precipitants
NDP
GAL
MPO
PLP
FS4
Exploring the Binding Modes of Ligands 11
Over 340 structures in the PDB have the co-factor Flavin Mononucleotide (FMN) bound to the protein
FMN displays considerable variation in
binding due to
the torsional flexibility in the molecule.
However, unique binding modes can be observed in proteins belonging to specific PFAM families.
Number of Structures
PF01070
PF01180 16 13
PF00258 17
PF00881 21 14
Total
Non-PSI
(Flavodoxin _1)
(FMN-dependent
dehydrogenase )
(Oxidored._FMN )
(DHOdehase )
(Flavin reductase-like)
(Nitroreductase)
(Pyridox._oxidase )