View source for 4ywu


==Structural insight into the substrate inhibition mechanism of NADP+-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes==
<StructureSection load='4ywu' size='340' side='right'caption='[[4ywu]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ywu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes_MGAS1882 Streptococcus pyogenes MGAS1882]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YWU 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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SSN:4-OXOBUTANOIC+ACID'>SSN</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=4ywu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ywu OCA], [https://pdbe.org/4ywu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ywu RCSB], [https://www.ebi.ac.uk/pdbsum/4ywu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ywu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0J9X1M8_STRPY A0A0J9X1M8_STRPY] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Succinic semialdehyde dehydrogenases (SSADHs) are ubiquitous enzymes that catalyze the oxidation of succinic semialdehyde (SSA) to succinic acid in the presence of NAD(P)+, and play an important role in the cellular mechanisms including the detoxification of accumulated SSA or the survival in conditions of limited nutrients. Here, we report the inhibitory properties and two crystal structures of SSADH from Streptococcus pyogenes (SpSSADH) in a binary (ES) complex with SSA as the substrate and a ternary (ESS) complex with the substrate SSA and the inhibitory SSA, at 2.4 A resolution for both structures. Analysis of the kinetic inhibitory parameters revealed significant substrate inhibition in the presence of NADP+ at concentrations of SSA higher than 0.02 mM, which exhibited complete uncompetitive substrate inhibition with the inhibition constant (Ki) value of 0.10 +/- 0.02 mM. In ES-complex of SpSSADH, the SSA showed a tightly bound bent form nearby the catalytic residues, which may be caused by reduction of the cavity volume for substrate binding, compared with other SSADHs. Moreover, structural comparison of ESS-complex with a binary complex with NADP+ of SpSSADH indicated that the substrate inhibition was induced by the binding of inhibitory SSA in the cofactor-binding site, instead of NADP+. Our results provide first structure-based molecular insights into the substrate inhibition mechanism of SpSSADH as the Gram-positive bacterial SSADH.

Structural insight into the substrate inhibition mechanism of NADP-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes.,Jang EH, Park SA, Chi YM, Lee KS Biochem Biophys Res Commun. 2015 Apr 16. pii: S0006-291X(15)00725-1. doi:, 10.1016/j.bbrc.2015.04.047. PMID:25888791<ref>PMID:25888791</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ywu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Succinate-semialdehyde dehydrogenase|Succinate-semialdehyde dehydrogenase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pyogenes MGAS1882]]
[[Category: Chi YM]]
[[Category: Jang EH]]
[[Category: Lee KS]]
[[Category: Park SA]]