PDBsum entry 3trc

Transferase

PDB id: 3trc

Contents

Protein chain

168 a.a.

Ligands

PO4

Metals

_NA

Waters ×193

PDB id:

3trc

Name:

Transferase

Title:

Structure of the gaf domain from a phosphoenolpyruvate-protein phosphotransferase (ptsp) from coxiella burnetii

Structure:

Phosphoenolpyruvate-protein phosphotransferase. Chain: a. Engineered: yes. Mutation: yes

Source:

Coxiella burnetii. Organism_taxid: 777. Strain: rsa493. Gene: cbu_1550, ptsp. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.65Å R-factor: 0.187 R-free: 0.214

Authors:

J.Cheung,M.C.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:

09-Sep-11 Release date: 28-Sep-11

Protein chain

Q83BF9  (Q83BF9_COXBU) -  phosphoenolpyruvate--protein phosphotransferase from Coxiella burnetii (strain RSA 493 / Nine Mile phase I)

Seq: 766 a.a.

Struc: 168 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.3.9 - phosphoenolpyruvate--protein phosphotransferase.
• Reaction: L-histidyl-[protein] + phosphoenolpyruvate = N(pros)-phospho-L-histidyl- [protein] + pyruvate

L-histidyl-[protein] + phosphoenolpyruvate (Bound ligand (Het Group name = PO4) matches with 50.00% similarity) = N(pros)-phospho-L-histidyl- [protein] + pyruvate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

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.