PDBsum entry 4ph6

Lyase

PDB id: 4ph6

Contents

Protein chains

240 a.a.

Waters ×311

PDB id:

4ph6

Name:

Lyase

Title:

Structure of 3-dehydroquinate dehydratase from enterococcus faecalis

Structure:

3-dehydroquinate dehydratase. Chain: a, b. Synonym: 3-dehydroquinase,type i dhqase. Engineered: yes

Source:

Enterococcus faecalis. Organism_taxid: 226185. Strain: atcc 700802 / v583. Gene: arod, ebsd, ef_1731. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.189 R-free: 0.255

Authors:

B.Xue,V.W.Cheung,W.S.Yew,R.C.Robinson

Key ref:

V.W.Cheung et al. (2014). Identification of polyketide inhibitors targeting 3-dehydroquinate dehydratase in the shikimate pathway of Enterococcus faecalis. Plos One, 9, e103598. PubMed id: 25072253 DOI: 10.1371/journal.pone.0103598

Date:

05-May-14 Release date: 17-Sep-14

Protein chains

P36923  (AROD_ENTFA) -  3-dehydroquinate dehydratase from Enterococcus faecalis (strain ATCC 700802 / V583)

Seq: 253 a.a.

Struc: 240 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.1.10 - 3-dehydroquinate dehydratase.
• Pathway: Shikimate and Chorismate Biosynthesis
• Reaction: 3-dehydroquinate = 3-dehydroshikimate + H2O

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

Added reference

DOI no: 10.1371/journal.pone.0103598

Plos One 9:e103598 (2014)

PubMed id: 25072253

Identification of polyketide inhibitors targeting 3-dehydroquinate dehydratase in the shikimate pathway of Enterococcus faecalis.

V.W.Cheung, B.Xue, M.Hernandez-Valladares, M.K.Go, A.Tung, A.H.Aguda, R.C.Robinson, W.S.Yew.

ABSTRACT

Due to the emergence of resistance toward current antibiotics, there is a pressing need to develop the next generation of antibiotics as therapeutics against infectious and opportunistic diseases of microbial origins. The shikimate pathway is exclusive to microbes, plants and fungi, and hence is an attractive and logical target for development of antimicrobial therapeutics. The Gram-positive commensal microbe, Enterococcus faecalis, is a major human pathogen associated with nosocomial infections and resistance to vancomycin, the "drug of last resort". Here, we report the identification of several polyketide-based inhibitors against the E. faecalis shikimate pathway enzyme, 3-dehydroquinate dehydratase (DHQase). In particular, marein, a flavonoid polyketide, both inhibited DHQase and retarded the growth of Enterococcus faecalis. The purification, crystallization and structural resolution of recombinant DHQase from E. faecalis (at 2.2 Å resolution) are also reported. This study provides a route in the development of polyketide-based antimicrobial inhibitors targeting the shikimate pathway of the human pathogen E. faecalis.