5uwv
From Proteopedia
(Difference between revisions)
m (Protected "5uwv" [edit=sysop:move=sysop]) |
|||
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Mycobacterium abscessus L,D-transpeptidase 2== | |
| + | <StructureSection load='5uwv' size='340' side='right'caption='[[5uwv]], [[Resolution|resolution]] 2.98Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5uwv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus_ATCC_19977 Mycobacteroides abscessus ATCC 19977]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UWV 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]] 2.98Å</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=5uwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uwv OCA], [https://pdbe.org/5uwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uwv RCSB], [https://www.ebi.ac.uk/pdbsum/5uwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uwv ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/B1MMQ4_MYCA9 B1MMQ4_MYCA9] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | As a growing number of clinical isolates of Mycobacterium abscessus are resistant to most antibiotics, new treatment options that are effective against these drug-resistant strains are desperately needed. The majority of the linkages in the cell wall peptidoglycan of M. abscessus are synthesized by non-classical transpeptidases, namely the L,D-transpeptidases. Emerging evidence suggests that these enzymes represent a new molecular vulnerability in this pathogen. Recent studies have demonstrated that inhibition of these enzymes by the carbapenem class of beta-lactams determines their activity against M. tuberculosis Here, we studied the interactions of beta-lactams with two L,D-transpeptidases in M. abscessus, namely LdtMab1 and LdtMab2, and found both the carbapenem and cephalosporin--but not penicillin-sub-class of beta-lactams inhibit these enzymes. Contrary to the commonly held belief that combination therapy with beta-lactams is redundant, doripenem and cefdinir exhibit synergy against both pan-susceptible M. abscessus and clinical isolates that are resistant to most antibiotics, which suggests that dual-beta-lactam therapy holds potential for treatment of M. abscessus Lastly, we solved the first crystal structure of an M. abscessus L,D-transpeptidase, LdtMab2, and using substitutions of critical amino acids in the catalytic site and computational simulations, we describe the key molecular interactions between this enzyme and beta-lactams, which provide an insight into the molecular basis for the relative efficacy of different beta-lactams against M. abscessus. | ||
| - | + | Mycobacterium abscessus L,D-transpeptidases are susceptible to inactivation by carbapenems and cephalosporins but not penicillins.,Kumar P, Chauhan V, Silva JRA, Lameira J, d'Andrea F, Li S, Ginell SL, Freundlich JS, Alves CN, Bailey S, Cohen KA, Lamichhane G Antimicrob Agents Chemother. 2017 Jul 31. pii: AAC.00866-17. doi:, 10.1128/AAC.00866-17. PMID:28760902<ref>PMID:28760902</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Ginell | + | <div class="pdbe-citations 5uwv" style="background-color:#fffaf0;"></div> |
| - | [[Category: Kumar | + | == References == |
| - | [[Category: Lamichhane | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacteroides abscessus ATCC 19977]] | ||
| + | [[Category: Ginell SL]] | ||
| + | [[Category: Kumar P]] | ||
| + | [[Category: Lamichhane G]] | ||
Current revision
Crystal structure of Mycobacterium abscessus L,D-transpeptidase 2
| |||||||||||
