9pcs
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Dihydrodipicolinate Synthase from Mycobacterium tuberculosis in complex with pyruvate== | |
| + | <StructureSection load='9pcs' size='340' side='right'caption='[[9pcs]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9pcs]] is a 8 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=9PCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PCS 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]] 1.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</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=9pcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pcs OCA], [https://pdbe.org/9pcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pcs RCSB], [https://www.ebi.ac.uk/pdbsum/9pcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pcs ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DAPA_MYCTU DAPA_MYCTU] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA) (Probable).<ref>PMID:18062777</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and is one of the leading causes of death worldwide. This disease is typically treated by combining several antimicrobials for extended periods, which can lead to treatment interruptions by patients and promote the emergence of multidrug-resistant strains, necessitating the use of alternative or second-line drugs. In this perspective, dihydrodipicolinate synthase (DapA) from M. tuberculosis (MtDapA), which catalyzes the aldol condensation between pyruvate and aspartate-semialdehyde (ASA) to produce dihydrodipicolinate, is an essential enzyme in Mtb for the production of l-lysine and meso-diaminopimelate (mDAP). Through crystallographic assays, we have determined the structure of MtDapA in complex with its substrate, pyruvate, covalently bonded through a Schiff base to the catalytic l-lysine at a resolution of 1.5 A. Through structural analysis, we describe the arrangement of interactions between the active site amino acid residues and pyruvate, providing insight into the binding mode of this molecule. In addition, we performed further biophysical assays, including differential scanning fluorimetry (DSF) and isothermal titration calorimetry (ITC), to obtain insights into the pyruvate affinity and the potential role of l-lysine and mDAP as allosteric regulators of MtDapA. However, in contrast to those observed in other orthologous enzymes, particularly those from Gram-negative bacteria, MtDapA does not have an affinity for l-lysine or mDAP. Consequently, this enzyme is not allosterically regulated by the products of this pathway. The results shown here provide evidence regarding the functioning of the enzyme regulatory mechanism and valuable structural features to aid in the future development of MtDapA inhibitors, which may be further explored in drug discovery campaigns against tuberculosis. | ||
| - | + | Crystal structure of dihydrodipicolinate synthase from Mycobacterium tuberculosis in complex with pyruvate and insights into allosteric regulation.,Rosa LVS, Blaszczyk B, Blundell T, Dias MVB Int J Biol Macromol. 2025 Sep 27;330(Pt 1):147950. doi: , 10.1016/j.ijbiomac.2025.147950. PMID:41022234<ref>PMID:41022234</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9pcs" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
| + | [[Category: Dias MVB]] | ||
| + | [[Category: Rosa LVS]] | ||
Current revision
Crystal structure of Dihydrodipicolinate Synthase from Mycobacterium tuberculosis in complex with pyruvate
| |||||||||||
