View source for 7ryt


==Crystal structure of Mycobacterium tuberculosis acetylated Homoserine transacetylase with Coenzyme A==
<StructureSection load='7ryt' size='340' side='right'caption='[[7ryt]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ryt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RYT 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]] 2.67&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=OAS:O-ACETYLSERINE'>OAS</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7ryt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ryt OCA], [https://pdbe.org/7ryt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ryt RCSB], [https://www.ebi.ac.uk/pdbsum/7ryt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ryt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/METXA_MYCTU METXA_MYCTU] Transfers an acetyl group from acetyl-CoA to L-homoserine, forming acetyl-L-homoserine.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mycobacterium tuberculosis (Mtb) lacking functional homoserine transacetylase (HTA) is compromised in methionine biosynthesis, protein synthesis, and in the activity of multiple essential S-adenosyl-l-methionine-dependent enzymes. Additionally, deficient mutants are further disarmed by the toxic accumulation of lysine due to a redirection of the metabolic flux toward the lysine biosynthetic pathway. Studies with deletion mutants and crystallographic studies of the apoenzyme have, respectively, validated Mtb HTA as an essential enzyme and revealed a ligandable binding site. Seeking a mechanistic characterization of this enzyme, we report crucial structural details and comprehensive functional characterization of Mtb HTA. Crystallographic and mass spectral observation of the acetylated HTA intermediate and initial velocity studies were consistent with a ping-pong kinetic mechanism. Wild-type HTA and its site-directed mutants were kinetically characterized with a panel of natural and alternative substrates to understand substrate specificity and identify critical residues for catalysis. Titration experiments using fluorescence quenching showed that both substrates horizontal line acetyl-CoA and l-homoserine horizontal line engage in a strong and weak binding interaction with HTA. Additionally, substrate inhibition by acetyl-CoA and product inhibition by CoA and O-acetyl-l-homoserine were proposed to form the basis of a feedback regulation mechanism. By furnishing key mechanistic and structural information, these studies provide a foundation for structure-based design efforts around this attractive Mtb target.

Structural and Functional Characterization of Mycobacterium tuberculosis Homoserine Transacetylase.,Sharma S, Jayasinghe YP, Mishra NK, Orimoloye MO, Wong TY, Dalluge JJ, Ronning DR, Aldrich CC ACS Infect Dis. 2023 Mar 10;9(3):540-553. doi: 10.1021/acsinfecdis.2c00541. Epub , 2023 Feb 8. PMID:36753622<ref>PMID:36753622</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ryt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Jayasinghe YP]]
[[Category: Ronning DR]]