View source for 6ok4


==Crystal Structure of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Chlamydia trachomatis with bound NAD==
<StructureSection load='6ok4' size='340' side='right'caption='[[6ok4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ok4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Chlamydia_trachomatis_D/UW-3/CX Chlamydia trachomatis D/UW-3/CX]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OK4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ok4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ok4 OCA], [https://pdbe.org/6ok4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ok4 RCSB], [https://www.ebi.ac.uk/pdbsum/6ok4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ok4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G3P_CHLTR 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]
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== 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<ref>PMID:31930578</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6ok4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glyceraldehyde-3-phosphate dehydrogenase 3D structures|Glyceraldehyde-3-phosphate dehydrogenase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Chlamydia trachomatis D/UW-3/CX]]
[[Category: Large Structures]]
[[Category: Structural genomic]]