PDBsum entry 3uwc

Transferase

PDB id: 3uwc

Contents

Protein chain

371 a.a.

Ligands

DIO

EDO

PMP

Metals

_NA ×3

Waters ×397

PDB id:

3uwc

Name:

Transferase

Title:

Structure of an aminotransferase (degt-dnrj-eryc1-strs family) from coxiella burnetii in complex with pmp

Structure:

Nucleotide-sugar aminotransferase. Chain: a. Engineered: yes

Source:

Coxiella burnetii. Organism_taxid: 777. Strain: rsa493. Gene: cbu_0696. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.80Å R-factor: 0.168 R-free: 0.188

Authors:

J.Cheung,M.Franklin,M.Rudolph,M.Cassidy,E.Gary,F.Burshteyn,J.Love

Key ref:

M.C.Franklin et al. (2015). Structural genomics for drug design against the pathogen Coxiella burnetii. Proteins, 83, 2124-2136. PubMed id: 26033498 DOI: 10.1002/prot.24841

Date:

01-Dec-11 Release date: 14-Dec-11

Protein chain

B5U8Q1  (B5U8Q1_COXBU) -  Nucleotide-sugar aminotransferase from Coxiella burnetii (strain RSA 493 / Nine Mile phase I)

Seq: 384 a.a.

Struc: 371 a.a.

Enzyme reactions

• Enzyme class: E.C.2.6.1.- - ?????

DOI no: 10.1002/prot.24841

Proteins 83:2124-2136 (2015)

PubMed id: 26033498

Structural genomics for drug design against the pathogen Coxiella burnetii.

M.C.Franklin, J.Cheung, M.J.Rudolph, F.Burshteyn, M.Cassidy, E.Gary, B.Hillerich, Z.K.Yao, P.R.Carlier, M.Totrov, J.D.Love.

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. Proteins 2015; 83:2124-2136. © 2015 Wiley Periodicals, Inc.