6ok4

Crystal Structure of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Chlamydia trachomatis with bound NAD

spinqualitylabelsall models 6ok4, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ok4 is a 4 chain structure with sequence from Chlamydia trachomatis D/UW-3/CX. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: CL, EDO, NAD, PEG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G3P_CHLTR Catalyzes the oxidative phosphorylation of glyceraldehyde 3-phosphate (G3P) to 1,3-bisphosphoglycerate (BPG) using the cofactor NAD. The first reaction step involves the formation of a hemiacetal intermediate between G3P and a cysteine residue, and this hemiacetal intermediate is then oxidized to a thioester, with concomitant reduction of NAD to NADH. The reduced NADH is then exchanged with the second NAD, and the thioester is attacked by a nucleophilic inorganic phosphate to produce BPG.[UniProtKB:P00362] Publication Abstract from PubMed 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. Structures of glyceraldehyde 3-phosphate dehydrogenase in Neisseria gonorrhoeae and Chlamydia trachomatis.,Barrett KF, Dranow DM, Phan IQ, Michaels SA, Shaheen S, Navaluna ED, Craig JK, Tillery LM, Choi R, Edwards TE, Conrady DG, Abendroth J, Horanyi PS, Lorimer DD, Van Voorhis WC, Zhang Z, Barrett LK, Subramanian S, Staker B, Fan E, Myler PJ, Soge OO, Hybiske K, Ojo KK Protein Sci. 2020 Mar;29(3):768-778. doi: 10.1002/pro.3824. Epub 2020 Jan 28. PMID:31930578 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glyceraldehyde-3-phosphate dehydrogenase 3D structures

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