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[[ | ==Crystal Structure of M. tuberculosis LD-transpeptidase type 2 with Modified Catalytic Cysteine (C354)== | ||
<StructureSection load='3vae' size='340' side='right' caption='[[3vae]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3vae]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VAE FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lppS, MT2594, Rv2518c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</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=3vae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vae OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vae RCSB], [http://www.ebi.ac.uk/pdbsum/3vae PDBsum]</span></td></tr> | |||
</table> | |||
<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 == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Amzel, L M | [[Category: Amzel, L M]] | ||
[[Category: Bianchet, M A | [[Category: Bianchet, M A]] | ||
[[Category: Erdemli, S | [[Category: Erdemli, S]] | ||
[[Category: Gupta, R | [[Category: Gupta, R]] | ||
[[Category: Lamichhane, G | [[Category: Lamichhane, G]] | ||
[[Category: Peptidoglycan binding protein]] | [[Category: Peptidoglycan binding protein]] | ||
[[Category: Protein-peptidoglycan complex]] | [[Category: Protein-peptidoglycan complex]] | ||
Revision as of 19:44, 9 December 2014
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
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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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