4nbq

Structure of the polynucleotide phosphorylase (CBU_0852) from Coxiella burnetii

spinqualitylabelsall models 4nbq, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nbq is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 NonStd Res: MSE Activity: Polyribonucleotide nucleotidyltransferase, with EC number 2.7.7.8 Resources: FirstGlance, OCA, RCSB, PDBsum Function [PNP_COXBU] Involved in mRNA degradation. Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'- to 5'-direction. Publication Abstract from PubMed 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 (hDFHR). 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. This article is protected by copyright. All rights reserved. Structural Genomics for Drug Design against the Pathogen Coxiella burnetii.,Franklin MC, Cheung J, Rudolph MJ, Burshteyn F, Cassidy M, Gary E, Hillerich B, Yao ZK, Carlier PR, Totrov M, Love JD Proteins. 2015 Jun 1. doi: 10.1002/prot.24841. PMID:26033498 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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