PDBsum entry 4nbq

Transferase

PDB id: 4nbq

Contents

Protein chains

659 a.a.

607 a.a.

Ligands

SO4 ×13

Waters ×12

PDB id:

4nbq

Name:

Transferase

Title:

Structure of the polynucleotide phosphorylase (cbu_0852) from coxiella burnetii

Structure:

Polyribonucleotide nucleotidyltransferase. Chain: a, b, c. Synonym: polynucleotide phosphorylase, pnpase. Engineered: yes

Source:

Coxiella burnetii. Organism_taxid: 227377. Strain: rsa 493 / nine mile phase i. Gene: pnp, cbu_0852. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.91Å R-factor: 0.211 R-free: 0.260

Authors:

M.J.Rudolph,J.Cheung,M.C.Franklin,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:

23-Oct-13 Release date: 17-Jun-15

Protein chains

Q83D87  (PNP_COXBU) -  Polyribonucleotide nucleotidyltransferase from Coxiella burnetii (strain RSA 493 / Nine Mile phase I)

Seq: 696 a.a.

Struc: 659 a.a.*

Protein chain

Q83D87  (PNP_COXBU) -  Polyribonucleotide nucleotidyltransferase from Coxiella burnetii (strain RSA 493 / Nine Mile phase I)

Seq: 696 a.a.

Struc: 607 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.2.7.7.8 - polyribonucleotide nucleotidyltransferase.
• Reaction: RNA(n+1) + phosphate = RNA(n) + a ribonucleoside 5'-diphosphate

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.