3vae: Difference between revisions
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<StructureSection load='3vae' size='340' side='right'caption='[[3vae]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='3vae' size='340' side='right'caption='[[3vae]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3vae]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3vae]] is a 2 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=3VAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VAE FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=3vae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vae OCA], [https://pdbe.org/3vae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vae RCSB], [https://www.ebi.ac.uk/pdbsum/3vae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vae ProSAT]</span></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=3vae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vae OCA], [https://pdbe.org/3vae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vae RCSB], [https://www.ebi.ac.uk/pdbsum/3vae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vae ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/LDT2_MYCTO LDT2_MYCTO] Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems. Is essential for virulence in a mouse model of acute infection.<ref>PMID:20305661</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Amzel | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Bianchet | [[Category: Amzel LM]] | ||
[[Category: Erdemli | [[Category: Bianchet MA]] | ||
[[Category: Gupta | [[Category: Erdemli S]] | ||
[[Category: Lamichhane | [[Category: Gupta R]] | ||
[[Category: Lamichhane G]] | |||
Latest revision as of 12:47, 30 October 2024
Crystal Structure of M. tuberculosis LD-transpeptidase type 2 with Modified Catalytic Cysteine (C354)Crystal Structure of M. tuberculosis LD-transpeptidase type 2 with Modified Catalytic Cysteine (C354)
Structural highlights
FunctionLDT2_MYCTO Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems. Is essential for virulence in a mouse model of acute infection.[1] Publication Abstract from PubMedWith multidrug-resistant cases of tuberculosis increasing globally, better antibiotic drugs and novel drug targets are becoming an urgent need. Traditional beta-lactam antibiotics that inhibit D,D-transpeptidases are not effective against mycobacteria, in part because mycobacteria rely mostly on L,D-transpeptidases for biosynthesis and maintenance of their peptidoglycan layer. This reliance plays a major role in drug resistance and persistence of Mycobacterium tuberculosis (Mtb) infections. The crystal structure at 1.7 A resolution of the Mtb L,D-transpeptidase Ldt(Mt2) containing a bound peptidoglycan fragment, reported here, provides information about catalytic site organization as well as substrate recognition by the enzyme. Based on our structural, kinetic, and calorimetric data, we propose a catalytic mechanism for Ldt(Mt2) in which both acyl-acceptor and acyl-donor substrates reach the catalytic site from the same, rather than different, entrances. Together, this information provides vital insights to facilitate development of drugs targeting this validated yet unexploited enzyme. Targeting the Cell Wall of Mycobacterium tuberculosis: Structure and Mechanism of L,D-Transpeptidase 2.,Erdemli SB, Gupta R, Bishai WR, Lamichhane G, Amzel LM, Bianchet MA Structure. 2012 Dec 5;20(12):2103-15. doi: 10.1016/j.str.2012.09.016. Epub 2012, Oct 25. PMID:23103390[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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