PDBsum entry 6ok4

Oxidoreductase

PDB id: 6ok4

Contents

Protein chains

334 a.a.

Ligands

NAD ×4

EDO ×15

PO4 ×6

PEG ×4

Metals

_CL

Waters ×430

PDB id:

6ok4

Name:

Oxidoreductase

Title:

Crystal structure of glyceraldehyde-3-phosphate dehydrogenase (gapdh) from chlamydia trachomatis with bound NAD

Structure:

Glyceraldehyde-3-phosphate dehydrogenase. Chain: a, b, c, d. Fragment: chtrb.00839.A.B1. Synonym: gapdh,NAD-dependent glyceraldehyde-3-phosphate dehydrogenase. Engineered: yes. Mutation: yes

Source:

Chlamydia trachomatis (strain d/uw-3/cx). Organism_taxid: 272561. Strain: d/uw-3/cx. Gene: gap, gapa, ct_505. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.40Å R-factor: 0.174 R-free: 0.208

Authors:

Seattle Structural Genomics Center For Infectious Disease (Ssgcid)

Key ref:

K.F.Barrett et al. (2020). Structures of glyceraldehyde 3-phosphate dehydrogenase in Neisseria gonorrhoeae and Chlamydia trachomatis. Protein Sci, 29, 768-778. PubMed id: 31930578 DOI: 10.1002/pro.3824

Date:

12-Apr-19 Release date: 24-Apr-19

Protein chains

P0CE13  (G3P_CHLTR) -  Glyceraldehyde-3-phosphate dehydrogenase from Chlamydia trachomatis serovar D (strain ATCC VR-885 / DSM 19411 / UW-3/Cx)

Seq: 334 a.a.

Struc: 334 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.2.1.12 - glyceraldehyde-3-phosphate dehydrogenase (phosphorylating).
• Pathway: Glyceraldehyde-3-phosphate Dehydrogenase (phosphorylating)
• Reaction: D-glyceraldehyde 3-phosphate + phosphate + NAD⁺ = (2R)-3-phospho- glyceroyl phosphate + NADH + H⁺

D-glyceraldehyde 3-phosphate + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly) + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = (2R)-3-phospho- glyceroyl phosphate + NADH + H(+)

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

reference

DOI no: 10.1002/pro.3824

Protein Sci 29:768-778 (2020)

PubMed id: 31930578

Structures of glyceraldehyde 3-phosphate dehydrogenase in Neisseria gonorrhoeae and Chlamydia trachomatis.

K.F.Barrett, D.M.Dranow, I.Q.Phan, S.A.Michaels, S.Shaheen, E.D.Navaluna, J.K.Craig, L.M.Tillery, R.Choi, T.E.Edwards, D.G.Conrady, J.Abendroth, P.S.Horanyi, D.D.Lorimer, W.C.Van Voorhis, Z.Zhang, L.K.Barrett, S.Subramanian, B.Staker, E.Fan, P.J.Myler, O.O.Soge, K.Hybiske, K.K.Ojo.

ABSTRACT

Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide and usually present as co-infections. Increasing resistance of Ng to currently recommended dual therapy of azithromycin and ceftriaxone presents therapeutic challenges for syndromic management of Ng-Ct co-infections. Development of a safe, effective, and inexpensive dual therapy for Ng-Ct co-infections is an effective strategy for the global control and prevention of these two most prevalent bacterial sexually transmitted infections. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a validated drug target with two approved drugs for indications other than antibacterials. Nonetheless, any new drugs targeting GAPDH in Ng and Ct must be specific inhibitors of bacterial GAPDH that do not inhibit human GAPDH, and structural information of Ng and Ct GAPDH will aid in finding such selective inhibitors. Here, we report the X-ray crystal structures of Ng and Ct GAPDH. Analysis of the structures demonstrates significant differences in amino acid residues in the active sites of human GAPDH from those of the two bacterial enzymes suggesting design of compounds to selectively inhibit Ng and Ct is possible. We also describe an efficient in vitro assay of recombinant GAPDH enzyme activity amenable to high-throughput drug screening to aid in identifying inhibitory compounds and begin to address selectivity.