4gsr

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:51, 20 March 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 1: Line 1:
==Structural basis for the inhibition of Mycobacterium tuberculosis L,D-transpeptidase by meropenem, a drug effective against extensively drug-resistant strains==
==Structural basis for the inhibition of Mycobacterium tuberculosis L,D-transpeptidase by meropenem, a drug effective against extensively drug-resistant strains==
-
<StructureSection load='4gsr' size='340' side='right' caption='[[4gsr]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
+
<StructureSection load='4gsr' size='340' side='right'caption='[[4gsr]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4gsr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GSR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GSR FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4gsr]] is a 1 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=4GSR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GSR FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EMT:2-(ETHYLMERCURI-THIO)-BENZOIC+ACID'>EMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gsq|4gsq]], [[4gsu|4gsu]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EMT:2-(ETHYLMERCURI-THIO)-BENZOIC+ACID'>EMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lppS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=4gsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsr OCA], [https://pdbe.org/4gsr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gsr RCSB], [https://www.ebi.ac.uk/pdbsum/4gsr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gsr ProSAT]</span></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=4gsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsr OCA], [http://pdbe.org/4gsr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gsr RCSB], [http://www.ebi.ac.uk/pdbsum/4gsr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gsr ProSAT]</span></td></tr>
+
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[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>
-
Difficulty in the treatment of tuberculosis and growing drug resistance in Mycobacterium tuberculosis (Mtb) are a global health issue. Carbapenems inactivate L,D-transpeptidases; meropenem, when administered with clavulanate, showed in vivo activity against extensively drug-resistant Mtb strains. LdtMt2 (Rv2518c), one of two functional L,D-transpeptidases in Mtb, is predominantly expressed over LdtMt1 (Rv0116c). Here, the crystal structure of N-terminally truncated LdtMt2 (residues Leu131-Ala408) is reported in both ligand-free and meropenem-bound forms. The structure of meropenem-inhibited LdtMt2 provides a detailed structural view of the interactions between a carbapenem drug and Mtb L,D-transpeptidase. The structures revealed that the catalytic L,D-transpeptidase domain of LdtMt2 is preceded by a bacterial immunogloblin-like Big_5 domain and is followed by an extended C-terminal tail that interacts with both domains. Furthermore, it is shown using mass analyses that meropenem acts as a suicide inhibitor of LdtMt2. Upon acylation of the catalytic Cys354 by meropenem, the `active-site lid' undergoes a large conformational change to partially cover the active site so that the bound meropenem is accessible to the bulk solvent via three narrow paths. This work will facilitate structure-guided discovery of L,D-transpeptidase inhibitors as novel antituberculosis drugs against drug-resistant Mtb.
+
-
 
+
-
Structural basis for the inhibition of Mycobacterium tuberculosis L,D-transpeptidase by meropenem, a drug effective against extensively drug-resistant strains.,Kim HS, Kim J, Im HN, Yoon JY, An DR, Yoon HJ, Kim JY, Min HK, Kim SJ, Lee JY, Han BW, Suh SW Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):420-31. doi:, 10.1107/S0907444912048998. Epub 2013 Feb 16. PMID:23519417<ref>PMID:23519417</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4gsr" style="background-color:#fffaf0;"></div>
+
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: An, D R]]
+
[[Category: Large Structures]]
-
[[Category: Han, B W]]
+
[[Category: Mycobacterium tuberculosis]]
-
[[Category: Im, H N]]
+
[[Category: An DR]]
-
[[Category: Kim, H S]]
+
[[Category: Han BW]]
-
[[Category: Kim, J]]
+
[[Category: Im HN]]
-
[[Category: Kim, J Y]]
+
[[Category: Kim HS]]
-
[[Category: Kim, S J]]
+
[[Category: Kim J]]
-
[[Category: Lee, J Y]]
+
[[Category: Kim JY]]
-
[[Category: Min, H K]]
+
[[Category: Kim S-J]]
-
[[Category: Suh, S W]]
+
[[Category: Lee JY]]
-
[[Category: Yoon, H J]]
+
[[Category: Min HK]]
-
[[Category: Yoon, J Y]]
+
[[Category: Suh SW]]
-
[[Category: D-transpeptidase]]
+
[[Category: Yoon HJ]]
-
[[Category: Transferase]]
+
[[Category: Yoon JY]]

Current revision

Structural basis for the inhibition of Mycobacterium tuberculosis L,D-transpeptidase by meropenem, a drug effective against extensively drug-resistant strains

PDB ID 4gsr

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gsr"
Personal tools