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< | ==E243 mutant of M. tuberculosis Rv3290C== | ||
<StructureSection load='2jjh' size='340' side='right'caption='[[2jjh]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2jjh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JJH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2JJH FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | |||
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jje|2jje]], [[2jjf|2jjf]], [[2jjg|2jjg]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lysine_6-transaminase L-lysine 6-transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.36 2.6.1.36] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2jjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jjh OCA], [http://pdbe.org/2jjh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jjh RCSB], [http://www.ebi.ac.uk/pdbsum/2jjh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jjh ProSAT]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jj/2jjh_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jjh ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lysine varepsilon-aminotransferase (LAT) converts lysine to alpha-aminoadipate-delta-semialdehyde in a PLP-mediated reaction. We mutated active-site T330, N328 and E243, and structurally rationalized their properties. T330A and T330S mutants cannot bind PLP and are inactive. N328A although inactive, binds to PLP. E243A retains activity, but binds alpha-ketoglutarate in a different conformation. We had earlier identified 2-aminomethyl piperidine derivative as a LAT inhibitor. The co-crystal structure reveals that it mimics binding of C5 substrates and exhibits two binding modes. E243, that shields R422 in the apo enzyme, exhibits conformational changes to permit the binding of the inhibitor in one of the binding modes. Structure-based analysis of bound water in the active site suggests optimization strategies for synthesis of improved inhibitors. | |||
Mutational analysis of Mycobacterium tuberculosis lysine varepsilon-aminotransferase and inhibitor co-crystal structures, reveals distinct binding modes.,Tripathi SM, Agarwal A, Ramachandran R Biochem Biophys Res Commun. 2015 Jul 17-24;463(1-2):154-60. doi:, 10.1016/j.bbrc.2015.05.055. Epub 2015 May 20. PMID:26003725<ref>PMID:26003725</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2jjh" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Aminotransferase 3D structures|Aminotransferase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: L-lysine 6-transaminase]] | [[Category: L-lysine 6-transaminase]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Ramachandran, R | [[Category: Ramachandran, R]] | ||
[[Category: Tripathi, S M | [[Category: Tripathi, S M]] | ||
[[Category: Aminotransferase]] | [[Category: Aminotransferase]] | ||
[[Category: E243a mutant]] | [[Category: E243a mutant]] | ||
| Line 26: | Line 46: | ||
[[Category: Rv3290c]] | [[Category: Rv3290c]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Latest revision as of 13:42, 16 September 2020
E243 mutant of M. tuberculosis Rv3290CE243 mutant of M. tuberculosis Rv3290C
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLysine varepsilon-aminotransferase (LAT) converts lysine to alpha-aminoadipate-delta-semialdehyde in a PLP-mediated reaction. We mutated active-site T330, N328 and E243, and structurally rationalized their properties. T330A and T330S mutants cannot bind PLP and are inactive. N328A although inactive, binds to PLP. E243A retains activity, but binds alpha-ketoglutarate in a different conformation. We had earlier identified 2-aminomethyl piperidine derivative as a LAT inhibitor. The co-crystal structure reveals that it mimics binding of C5 substrates and exhibits two binding modes. E243, that shields R422 in the apo enzyme, exhibits conformational changes to permit the binding of the inhibitor in one of the binding modes. Structure-based analysis of bound water in the active site suggests optimization strategies for synthesis of improved inhibitors. Mutational analysis of Mycobacterium tuberculosis lysine varepsilon-aminotransferase and inhibitor co-crystal structures, reveals distinct binding modes.,Tripathi SM, Agarwal A, Ramachandran R Biochem Biophys Res Commun. 2015 Jul 17-24;463(1-2):154-60. doi:, 10.1016/j.bbrc.2015.05.055. Epub 2015 May 20. PMID:26003725[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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