View source for 4zfq


==Structure of M. tuberculosis (3,3) L,D-Transpeptidase, LdtMt5. (Meropenen-adduct form)==
<StructureSection load='4zfq' size='340' side='right'caption='[[4zfq]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zfq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. 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 [https://proteopedia.org/fgij/fg.htm?mol=4ZFQ 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]] 2.799&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zfq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zfq OCA], [https://pdbe.org/4zfq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zfq RCSB], [https://www.ebi.ac.uk/pdbsum/4zfq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zfq ProSAT]</span></td></tr>
</table>
== Function ==
[https://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 ==
The final step of peptidoglycan (PG) biosynthesis in bacteria involves crosslinking of peptide side chains. This step in Mycobacterium tuberculosis is catalyzed by L,D- and D,D-transpeptidases that generate 3--&gt;3 and 4--&gt;3 transpeptide linkages, respectively. M. tuberculosis PG is predominantly 3--&gt;3 crosslinked and LdtMt2 is the dominant L,D-transpeptidase. There are four additional sequence paralogs of LdtMt2 encoded by the genome of this pathogen and the reason for this apparent redundancy is unknown. Here, we have studied one of the paralogs, LdtMt5, and found it to be structurally and functionaly distinct. The structures of apo-LdtMt5 and its Meropenem adduct presented here demonstrate that, despite overall architectural similarity to LdtMt2, the LdtMt5 active site has marked differences. The presence of a structurally divergent catalytic site and a proline-rich C-terminal subdomain suggest this protein may have a distinct role in PG metabolism, perhaps involving other cell wall-anchored proteins. Further, M. tuberculosis lacking a functional copy of LdtMt5 displays aberrant growth, and is more susceptible to killing by crystal violet, osmotic shock, and select carbapenem antibiotics. Therefore, we conclude LdtMt5 is not a functionally redundant L,D-transpeptidase, but rather it serves a unique and important role in maintaining the integrity of the M. tuberculosis cell wall.

Loss of a functionally and structurally distinct L,D-transpeptidase, LdtMt5, compromises cell wall integrity in Mycobacterium tuberculosis.,Brammer Basta LA, Ghosh A, Pan Y, Jean J, Lloyd EP, Townsend CA, Lamichhane G, Bianchet MA J Biol Chem. 2015 Aug 24. pii: jbc.M115.660753. PMID:26304120<ref>PMID:26304120</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zfq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis CDC1551]]
[[Category: Basta L]]
[[Category: Bianchet MA]]
[[Category: Ghosh A]]
[[Category: Lamichhane G]]