View source for 4rjy


==Crystal structure of E. coli L-Threonine Aldolase in complex with a non-covalently uncleaved bound L-serine substrate==
<StructureSection load='4rjy' size='340' side='right'caption='[[4rjy]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rjy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_KTE79 Escherichia coli KTE79]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RJY 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SER:SERINE'>SER</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=4rjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rjy OCA], [https://pdbe.org/4rjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rjy RCSB], [https://www.ebi.ac.uk/pdbsum/4rjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rjy ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
l-Threonine aldolases (TAs), a family of enzymes belonging to the fold-type I pyridoxal 5'-phosphate (PLP) dependent enzymes, play a role in catalyzing the reversible cleavage of l-3-hydroxy-alpha-amino acids to glycine and the corresponding aldehydes. Threonine aldolases have great biotechnological potential for the syntheses of pharmaceutically relevant drug molecules because of their stereospecificity. The pH-dependency of their catalytic activity, affecting reaction intermediates, led us to study the effect of low-pH on Escherichia coli TA (eTA) structure. We report here a low-pH crystal structure of eTA at 2.1A resolution, with a non-covalently bound uncleaved l-serine substrate, and a PLP cofactor bound as an internal aldimine. This structure contrasts with other eTA structures obtained at physiological pH that show products or substrates bound as PLP-external aldimines. The non-productive binding at low-pH is due to an unusual substrate serine binding orientation in which the alpha-amino group and carboxylate group are in the wrong positions (relative to the active site residues) as a result of protonation of the alpha-amino group of the serine, as well as the active site histidines, His83 and His126. Protonation of these residues prevents the characteristic nucleophilic attack of the alpha-amino group of substrate serine on C4' of PLP to form the external aldimine. Our study shows that at low pH the change in charge distribution at the active site can result in substrates binding in a non-productive orientation.

Molecular basis of E. colil-threonine aldolase catalytic inactivation at low pH.,Remesh SG, Ghatge MS, Ahmed MH, Musayev FN, Gandhi A, Chowdhury N, di Salvo ML, Kellogg GE, Contestabile R, Schirch V, Safo MK Biochim Biophys Acta. 2015 Jan 2;1854(4):278-283. doi:, 10.1016/j.bbapap.2014.12.023. PMID:25560296<ref>PMID:25560296</ref>

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

==See Also==
*[[Aldolase 3D structures|Aldolase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli KTE79]]
[[Category: Large Structures]]
[[Category: Chowdhury N]]
[[Category: Gandhi AK]]
[[Category: Safo MK]]