View source for 6fzh


==Crystal structure of a streptococcal dehydrogenase at 1.5 Angstroem resolution==
<StructureSection load='6fzh' size='340' side='right'caption='[[6fzh]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fzh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Strp8 Strp8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FZH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FZH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gap, gapA, plr, spyM18_0261 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186103 STRP8])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fzh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fzh OCA], [http://pdbe.org/6fzh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fzh RCSB], [http://www.ebi.ac.uk/pdbsum/6fzh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fzh ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/G3P_STRP8 G3P_STRP8]] 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] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ubiquitous and highly abundant glycolytic enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pivotal for the energy and carbon metabolism of most organisms, including human pathogenic bacteria. For bacteria that depend mostly on glycolysis for survival, GAPDH is an attractive target for inhibitor discovery. The availability of high-resolution structures of GAPDH from various pathogenic bacteria is central to the discovery of new antibacterial compounds. We have determined the X-ray crystal structures of two new GAPDH enzymes from Gram-positive bacterial pathogens, Streptococcus pyogenes and Clostridium perfringens. These two structures, and the recent structure of Atopobium vaginae GAPDH, reveal details in the active site that can be exploited for the design of novel inhibitors based on naturally occurring molecules. Two such molecules, anacardic acid and curcumin, have been found to counter bacterial infection in clinical settings, although the cellular targets responsible for their antimicrobial properties remain unknown. We show that both anacardic acid and curcumin inhibit GAPDH from two bacterial pathogens through uncompetitive and non-competitive mechanisms, suggesting GAPDH as a relevant pharmaceutical target for antibacterial development. Inhibition of GAPDH by anacardic acid and curcumin seems to be unrelated to the immune evasion function of pathogenic bacterial GAPDH, since neither natural compound interfere with binding to the human C5a anaphylatoxin.

The Antimicrobials Anacardic Acid and Curcumin Are Not-Competitive Inhibitors of Gram-Positive Bacterial Pathogenic Glyceraldehyde-3-Phosphate Dehydrogenase by a Mechanism Unrelated to Human C5a Anaphylatoxin Binding.,Gomez S, Querol-Garcia J, Sanchez-Barron G, Subias M, Gonzalez-Alsina A, Franco-Hidalgo V, Alberti S, Rodriguez de Cordoba S, Fernandez FJ, Vega MC Front Microbiol. 2019 Feb 26;10:326. doi: 10.3389/fmicb.2019.00326. eCollection, 2019. PMID:30863383<ref>PMID:30863383</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fzh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Strp8]]
[[Category: Alberti, S]]
[[Category: Cordoba, S Rodriguez de]]
[[Category: Fernandez, F J]]
[[Category: Franco-Hidalgo, V]]
[[Category: Gomez, S]]
[[Category: Gonzalez-Alsina, A]]
[[Category: Melchor-Tafur, C]]
[[Category: Querol-Garcia, J]]
[[Category: Sanchez-Barron, G]]
[[Category: Subias, M]]
[[Category: Vega, M C]]
[[Category: Anacardic acid]]
[[Category: C3]]
[[Category: C3a]]
[[Category: C5a]]
[[Category: Complement]]
[[Category: Curcumin]]
[[Category: Dehydrogenase]]
[[Category: Gapdh]]
[[Category: Nad]]
[[Category: Oxidoreductase]]
[[Category: Streptococcus pyogene]]