6d5a: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 6d5a is ~~ON HOLD~~ ~~until Paper~~ Publication

==Crystal structure of L,D-transpeptidase 5 from Mycobacterium tuberculosis in apo form==

== Structural highlights ==

<table><tr><td colspan='2'>[[6d5a]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D5A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D5A FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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=6d5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d5a OCA], [http://pdbe.org/6d5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d5a RCSB], [http://www.ebi.ac.uk/pdbsum/6d5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d5a ProSAT]</span></td></tr>

</table>

== Function ==

[[http://www.uniprot.org/uniprot/LDT5_MYCTU LDT5_MYCTU]] 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.<ref>PMID:24041897</ref>

== Publication Abstract from PubMed ==

Targeting Mycobacterium tuberculosis peptidoglycans with beta-lactam antibiotics represents a strategy to address increasing resistance to antitubercular drugs. beta-Lactams inhibit peptidoglycan synthases such as l,d-transpeptidases, a group of carbapenem-sensitive enzymes that stabilize peptidoglycans through 3 --> 3 cross-links. M. tuberculosis encodes five l,d-transpeptidases (LdtMt1-5), of which LdtMt3 is one of the less understood. Herein, we structurally characterized the apo and faropenem-acylated forms of LdtMt3 at 1.3 and 1.8 A resolution, respectively. These structures revealed a fold and catalytic diad similar to those of other LdtsMt enzymes, supporting its involvement in transpeptidation reactions despite divergences in active site size and charges. The LdtMt3-faropenem structure indicated that faropenem is degraded after Cys-246 acylation, and possibly only a beta-OH-butyrate or an acetyl group (C2H3O) covalently attached to the enzyme remains, an observation that strongly supports the notion that LdtMt3 is inactivated by beta-lactams. Docking simulations with intact beta-lactams predicted key LdtMt3 residues that interact with these antibiotics. We also characterized the heat of acylation involved in the binding and reaction of LdtMt3 for ten beta-lactams belonging to four different classes, and imipenem had the highest inactivation constant. This work provides key insights into the structure, binding mechanisms, and degradation of beta-lactams by LdtMt3, which may be useful for the development of additional beta-lactams with potential antitubercular activity.

~~Authors~~:

Structural Basis for the Interaction and Processing of beta-Lactam Antibiotics by l,d-Transpeptidase 3 (LdtMt3) from Mycobacterium tuberculosis.,Libreros-Zuniga GA, Dos Santos Silva C, Salgado Ferreira R, Dias MVB ACS Infect Dis. 2019 Feb 8;5(2):260-271. doi: 10.1021/acsinfecdis.8b00244. Epub, 2018 Dec 28. PMID:30556998<ref>PMID:30556998</ref>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased Structures~~]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Dias, M V]]

[[Category: Libreros, G A]]

[[Category: Apo form]]

[[Category: D transpeptidation]]

[[Category: Transferase]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6d5a is ON HOLD  until Paper Publication
+==Crystal structure of L,D-transpeptidase 5 from Mycobacterium tuberculosis in apo form==
+<StructureSection load='6d5a' size='340' side='right' caption='[[6d5a]], [[Resolution|resolution]] 2.62&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6d5a]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D5A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D5A FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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=6d5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d5a OCA], [http://pdbe.org/6d5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d5a RCSB], [http://www.ebi.ac.uk/pdbsum/6d5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d5a ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/LDT5_MYCTU LDT5_MYCTU]] 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.<ref>PMID:24041897</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Targeting Mycobacterium tuberculosis peptidoglycans with beta-lactam antibiotics represents a strategy to address increasing resistance to antitubercular drugs. beta-Lactams inhibit peptidoglycan synthases such as l,d-transpeptidases, a group of carbapenem-sensitive enzymes that stabilize peptidoglycans through 3 --&gt; 3 cross-links. M. tuberculosis encodes five l,d-transpeptidases (LdtMt1-5), of which LdtMt3 is one of the less understood. Herein, we structurally characterized the apo and faropenem-acylated forms of LdtMt3 at 1.3 and 1.8 A resolution, respectively. These structures revealed a fold and catalytic diad similar to those of other LdtsMt enzymes, supporting its involvement in transpeptidation reactions despite divergences in active site size and charges. The LdtMt3-faropenem structure indicated that faropenem is degraded after Cys-246 acylation, and possibly only a beta-OH-butyrate or an acetyl group (C2H3O) covalently attached to the enzyme remains, an observation that strongly supports the notion that LdtMt3 is inactivated by beta-lactams. Docking simulations with intact beta-lactams predicted key LdtMt3 residues that interact with these antibiotics. We also characterized the heat of acylation involved in the binding and reaction of LdtMt3 for ten beta-lactams belonging to four different classes, and imipenem had the highest inactivation constant. This work provides key insights into the structure, binding mechanisms, and degradation of beta-lactams by LdtMt3, which may be useful for the development of additional beta-lactams with potential antitubercular activity.
-Authors:
+Structural Basis for the Interaction and Processing of beta-Lactam Antibiotics by l,d-Transpeptidase 3 (LdtMt3) from Mycobacterium tuberculosis.,Libreros-Zuniga GA, Dos Santos Silva C, Salgado Ferreira R, Dias MVB ACS Infect Dis. 2019 Feb 8;5(2):260-271. doi: 10.1021/acsinfecdis.8b00244. Epub, 2018 Dec 28. PMID:30556998<ref>PMID:30556998</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6d5a" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Dias, M V]]
+[[Category: Libreros, G A]]
+[[Category: Apo form]]
+[[Category: D transpeptidation]]
+[[Category: Transferase]]