5l2f: Difference between revisions

Line 1:

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

The ~~entry 5l2f~~ is ~~ON HOLD~~

==High Resolution Structure of Acinetobacter baumannii beta-lactamase OXA-51 I129L/K83D bound to doripenem==

== Structural highlights ==

<table><tr><td colspan='2'>[[5l2f]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L2F FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4J6:(4R,5S)-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-3-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>4J6</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kzh|5kzh]]</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=5l2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l2f OCA], [http://pdbe.org/5l2f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l2f RCSB], [http://www.ebi.ac.uk/pdbsum/5l2f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l2f ProSAT]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

OXA-51 is a class D beta-lactamase that is thought to be the native carbapenemase of Acinetobacter baumannii. Many variants of OXA-51 containing active site substitutions have been identified from A. baumannii isolates, and some of these substitutions increase hydrolytic activity toward carbapenem antibiotics. We have determined the high-resolution structures of apo OXA-51 and OXA-51 with one such substitution (I129L) with the carbapenem doripenem trapped in the active site as an acyl-intermediate. The structure shows that acyl-doripenem adopts an orientation very similar to carbapenem ligands observed in the active site of OXA-24/40 (doripenem) and OXA-23 (meropenem). In the OXA-51 variant/doripenem complex, the indole ring of W222 is oriented away from the doripenem binding site, thereby eliminating a clash that is predicted to occur in wildtype OXA-51. Similarly, in the OXA-51 variant complex, L129 adopts a different rotamer compared to I129 in wildtype OXA-51. This alternative position moves its side chain away from the hydroxyethyl moiety of doripenem and relieves another potential clash between the enzyme and carbapenem substrates. Molecular dynamics simulations of OXA-51 and OXA-51 I129L demonstrate that compared to isoleucine, a leucine at this position greatly favors a rotamer that accommodates the ligand. These results provide a molecular justification for how this substitution generates enhanced binding affinity for carbapenems, and therefore helps explain the prevalence of this substitution in clinical OXA-51 variants.

~~Authors~~:

The structure of a doripenem-bound OXA-51 class D beta-lactamase variant with enhanced carbapenemase activity.,June CM, Muckenthaler TJ, Schroder EC, Klamer ZL, Wawrzak Z, Powers RA, Szarecka A, Leonard DA Protein Sci. 2016 Sep 16. doi: 10.1002/pro.3040. PMID:27636561<ref>PMID:27636561</ref>

~~Description~~:

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

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

</div>

== References ==

__TOC__

</StructureSection>

[[Category: June, C M]]

[[Category: Leonard, D A]]

[[Category: Muckenthaler, T]]

[[Category: Powers, R A]]

[[Category: Antibiotic]]

[[Category: Beta-lactamase]]

[[Category: Hydrolase]]

[[Category: Hydrolase-antibiotic complex]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5l2f is ON HOLD
+==High Resolution Structure of Acinetobacter baumannii beta-lactamase OXA-51 I129L/K83D bound to doripenem==
+<StructureSection load='5l2f' size='340' side='right' caption='[[5l2f]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5l2f]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L2F FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4J6:(4R,5S)-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-3-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>4J6</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kzh|5kzh]]</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=5l2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l2f OCA], [http://pdbe.org/5l2f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l2f RCSB], [http://www.ebi.ac.uk/pdbsum/5l2f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l2f ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+OXA-51 is a class D beta-lactamase that is thought to be the native carbapenemase of Acinetobacter baumannii. Many variants of OXA-51 containing active site substitutions have been identified from A. baumannii isolates, and some of these substitutions increase hydrolytic activity toward carbapenem antibiotics. We have determined the high-resolution structures of apo OXA-51 and OXA-51 with one such substitution (I129L) with the carbapenem doripenem trapped in the active site as an acyl-intermediate. The structure shows that acyl-doripenem adopts an orientation very similar to carbapenem ligands observed in the active site of OXA-24/40 (doripenem) and OXA-23 (meropenem). In the OXA-51 variant/doripenem complex, the indole ring of W222 is oriented away from the doripenem binding site, thereby eliminating a clash that is predicted to occur in wildtype OXA-51. Similarly, in the OXA-51 variant complex, L129 adopts a different rotamer compared to I129 in wildtype OXA-51. This alternative position moves its side chain away from the hydroxyethyl moiety of doripenem and relieves another potential clash between the enzyme and carbapenem substrates. Molecular dynamics simulations of OXA-51 and OXA-51 I129L demonstrate that compared to isoleucine, a leucine at this position greatly favors a rotamer that accommodates the ligand. These results provide a molecular justification for how this substitution generates enhanced binding affinity for carbapenems, and therefore helps explain the prevalence of this substitution in clinical OXA-51 variants.
-Authors:
+The structure of a doripenem-bound OXA-51 class D beta-lactamase variant with enhanced carbapenemase activity.,June CM, Muckenthaler TJ, Schroder EC, Klamer ZL, Wawrzak Z, Powers RA, Szarecka A, Leonard DA Protein Sci. 2016 Sep 16. doi: 10.1002/pro.3040. PMID:27636561<ref>PMID:27636561</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 5l2f" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: June, C M]]
+[[Category: Leonard, D A]]
+[[Category: Muckenthaler, T]]
+[[Category: Powers, R A]]
+[[Category: Antibiotic]]
+[[Category: Beta-lactamase]]
+[[Category: Hydrolase]]
+[[Category: Hydrolase-antibiotic complex]]