4zfq: Difference between revisions
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''' | ==Structure of M. tuberculosis (3,3) L,D-Transpeptidase, LdtMt5. (Meropenen-adduct form)== | ||
<StructureSection load='4zfq' size='340' side='right' caption='[[4zfq]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4zfq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZFQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZFQ FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DWZ:(2S,3R,4S)-4-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-2-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-METHYL-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>DWZ</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4z7a|4z7a]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zfq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zfq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zfq RCSB], [http://www.ebi.ac.uk/pdbsum/4zfq PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/LDT5_MYCTO LDT5_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 (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
With 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<ref>PMID:23103390</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Basta, L]] | |||
[[Category: Bianchet, M A]] | |||
[[Category: Ghosh, A]] | |||
[[Category: Lamichhane, G]] | [[Category: Lamichhane, G]] | ||
[[Category: | [[Category: Carbapenem]] | ||
[[Category: | [[Category: Cell wall biosynthesis]] | ||
[[Category: | [[Category: L d-transpeptidase]] | ||
[[Category: Mycobaterium tuberculosis]] | |||
[[Category: Peptidoglycan linkage]] | |||
[[Category: Transferase]] | |||
Revision as of 12:25, 2 September 2015
Structure of M. tuberculosis (3,3) L,D-Transpeptidase, LdtMt5. (Meropenen-adduct form)
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