View source for 26fv


==Tetrameric cystathionine beta-synthase of Mycobacterium tuberculosis bound to AOAA==
<StructureSection load='26fv' size='340' side='right'caption='[[26fv]], [[Resolution|resolution]] 3.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[26fv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=26FV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=26FV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.34&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IK2:4-DEOXY-4-ACETYLYAMINO-PYRIDOXAL-5-PHOSPHATE'>IK2</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=26fv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=26fv OCA], [https://pdbe.org/26fv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=26fv RCSB], [https://www.ebi.ac.uk/pdbsum/26fv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=26fv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CBS_MYCTU CBS_MYCTU] Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine (PubMed:35749503). This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (PubMed:35749503). Also capable of generating lanthionine and hydrogen sulfide (PubMed:35749503).<ref>PMID:35749503</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tuberculosis (TB) remains a major global health threat, with Mycobacterium tuberculosis (Mtb) infecting nearly a quarter of the global population. Drug-resistant TB and HIV-TB co-infections emphasize the need for novel therapeutic approaches targeting essential metabolic pathways. Here, we investigated Mtb cystathionine beta-synthase (MtbCBS), a pyridoxal 5'-phosphate (PLP) dependent enzyme critical for sulfur metabolism and redox regulation, owing to its potential as a therapeutic target. Despite growing efforts to develop novel therapeutics, the widely used inhibitor aminooxy acetic acid (AOAA) is a non-specific inhibitor of all PLP-dependent enzymes, and the precise structural and mechanistic basis for its activity and specificity remains poorly understood. We present the high-resolution cryo-EM structure of full-length tetrameric MtbCBS in complex with AOAA, revealing a stable PLP-inhibitor adduct stabilized by two highly conserved active-site residues, T75 and Q147. This integrated approach employs cryo-EM, molecular dynamics (MD) simulations, Density Functional Theory (DFT) calculations, and comparative inhibition studies to reveal the molecular basis and determinants governing PLP-enzyme MtbCBS inhibition by AOAA. Through molecular mimic studies, we identified precise structural and electronic features of the inhibitor candidate that are critical for inhibition efficiency. These findings provide a mechanistic rationale for MtbCBS inhibition, and the unexplored roles of these key residues can be considered in the design of next-generation inhibitors targeting CBS enzymes implicated in infectious diseases, cancer, and neurological disorders.

Molecular insights into inhibitor action on the catalytic activity of Mycobacterium tuberculosis cystathionine beta-synthase enzyme.,Polepalli S, Roy A, Mondal B, Singh A, Dutta S Int J Biol Macromol. 2026 Aug 10;381(Pt 1):154013. doi: , 10.1016/j.ijbiomac.2026.154013. PMID:42575362<ref>PMID:42575362</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 26fv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Dutta S]]
[[Category: Mondal B]]
[[Category: Polepalli S]]
[[Category: Roy A]]