3TQZ

Structure of a deoxyuridine 5'-triphosphate nucleotidohydrolase (dut) from Coxiella burnetii

3TQZ の概要

• エントリーDOI: 10.2210/pdb3tqz/pdb
• 分子名称: Deoxyuridine 5'-triphosphate nucleotidohydrolase, SULFATE ION (3 entities in total)
• 機能のキーワード: purines, pyrimidines, nucleosides, nucleotides, hydrolase
• 由来する生物種: Coxiella burnetii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16883.80

構造登録者

Cheung, J.,Franklin, M.,Rudolph, M.,Cassidy, M.,Gary, E.,Burshteyn, F.,Love, J. (登録日: 2011-09-09, 公開日: 2011-09-21, 最終更新日: 2024-10-16)

主引用文献

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

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: 26033498
DOI: 10.1002/prot.24841

実験手法

X-RAY DIFFRACTION (1.75 Å)