3TQR
Structure of the phosphoribosylglycinamide formyltransferase (purN) in complex with CHES from Coxiella burnetii
Summary for 3TQR
| Entry DOI | 10.2210/pdb3tqr/pdb |
| Descriptor | Phosphoribosylglycinamide formyltransferase, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | purines, pyrimidines, nucleosides, nucleotides, transferase |
| Biological source | Coxiella burnetii |
| Total number of polymer chains | 1 |
| Total formula weight | 24211.71 |
| Authors | Rudolph, M.,Cheung, J.,Franklin, M.C.,Cassidy, M.,Gary, E.,Burshteyn, F.,Love, J. (deposition date: 2011-09-09, release date: 2011-09-28, Last modification date: 2024-10-16) |
| Primary citation | Franklin, M.C.,Cheung, J.,Rudolph, M.J.,Burshteyn, F.,Cassidy, M.,Gary, E.,Hillerich, B.,Yao, Z.K.,Carlier, P.R.,Totrov, M.,Love, J.D. Structural genomics for drug design against the pathogen Coxiella burnetii. Proteins, 83:2124-2136, 2015 Cited by PubMed Abstract: Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C. burnetii that have great potential as drug targets. We used high-throughput techniques to produce novel crystal structures of 48 of these proteins. We selected one protein, C. burnetii dihydrofolate reductase (CbDHFR), for additional work to demonstrate the value of these structures for structure-based drug design. This enzyme's structure reveals a feature in the substrate binding groove that is different between CbDHFR and human dihydrofolate reductase (hDHFR). We then identified a compound by in silico screening that exploits this binding groove difference, and demonstrated that this compound inhibits CbDHFR with at least 25-fold greater potency than hDHFR. Since this binding groove feature is shared by many other prokaryotes, the compound identified could form the basis of a novel antibacterial agent effective against a broad spectrum of pathogenic bacteria. PubMed: 26033498DOI: 10.1002/prot.24841 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.97 Å) |
Structure validation
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