OCA at 15:59, 27 February 2019

OCA — Wed, 27 Feb 2019 15:59:28 GMT

←Older revision		Revision as of 15:59, 27 February 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6h2i is ~~ON HOLD~~	+	==Structure of BlaC from Mycobacterium tuberculosis bound to the trans-enamine adduct of tazobactam.==
		+	<StructureSection load='6h2i' size='340' side='right' caption='[[6h2i]], [[Resolution\|resolution]] 2.72Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6h2i]] is a 2 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=6H2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H2I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=TBE:TAZOBACTAM+INTERMEDIATE'>TBE</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaC, ERS027646_02769 ([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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </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=6h2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h2i OCA], [http://pdbe.org/6h2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h2i RCSB], [http://www.ebi.ac.uk/pdbsum/6h2i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h2i ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Mycobacterium tuberculosis (Mtb), the main causative agent of tuberculosis (TB), is naturally resistant to beta-lactam antibiotics due to the production of the extended spectrum beta-lactamase BlaC. beta-Lactam/beta-lactamase inhibitor combination therapies can circumvent the BlaC-mediated resistance of Mtb and are promising treatment options against TB. However, still little is known of the exact mechanism of BlaC inhibition by the beta-lactamase inhibitors currently approved for clinical use, clavulanic acid, sulbactam, tazobactam, and avibactam. Here, we present the X-ray diffraction crystal structures of the acyl-enzyme adducts of wild-type BlaC with the four inhibitors. The +70 Da adduct derived from clavulanate and the trans-enamine acylation adducts of sulbactam and tazobactam are reported. BlaC in complex with avibactam revealed two inhibitor conformations. Preacylation binding could not be observed because inhibitor binding was not detected in BlaC variants carrying a substitution of the active site serine 70 to either alanine or cysteine, by crystallography, ITC or NMR. These results suggest that the catalytic serine 70 is necessary not only for enzyme acylation but also for increasing BlaC affinity for inhibitors in the preacylation state. The structure of BlaC with the serine to cysteine mutation showed a covalent linkage of the cysteine 70 Sgamma atom to the nearby amino group of lysine 73. The differences of adduct conformations between BlaC and other beta-lactamases are discussed.

-	~~Authors: Tassoni~~, R., Pannu, N.S., ~~Ubbink, M~~.	+	New Conformations of Acylation Adducts of Inhibitors of beta-Lactamase from Mycobacterium tuberculosis.,Tassoni R, Blok A, Pannu NS, Ubbink M Biochemistry. 2019 Feb 19;58(7):997-1009. doi: 10.1021/acs.biochem.8b01085. Epub , 2019 Jan 30. PMID:30632739<ref>PMID:30632739</ref>

-	~~Description: Structure~~ of ~~BlaC from Mycobacterium tuberculosis bound to~~ the ~~trans-enamine adduct~~ of ~~tazobactam~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6h2i" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Pannu, N S]]
	[[Category: Tassoni, R]]		[[Category: Tassoni, R]]
	[[Category: Ubbink, M]]		[[Category: Ubbink, M]]
-	[[Category: ~~Pannu, N.S~~]]	+	[[Category: Hydrolase]]

OCA: Protected "6h2i" [edit=sysop:move=sysop]

OCA — Wed, 25 Jul 2018 06:02:49 GMT

Protected "6h2i" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:02, 25 July 2018

OCA: New page: '''Unreleased structure''' The entry 6h2i is ON HOLD Authors: Tassoni, R., Pannu, N.S., Ubbink, M. Description: Structure of BlaC from Mycobacterium tuberculosis bound to the trans-ena...

OCA — Wed, 25 Jul 2018 06:02:48 GMT

New page: '''Unreleased structure''' The entry 6h2i is ON HOLD Authors: Tassoni, R., Pannu, N.S., Ubbink, M. Description: Structure of BlaC from Mycobacterium tuberculosis bound to the trans-ena...

New page

'''Unreleased structure'''

The entry 6h2i is ON HOLD

Authors: Tassoni, R., Pannu, N.S., Ubbink, M.

Description: Structure of BlaC from Mycobacterium tuberculosis bound to the trans-enamine adduct of tazobactam.
[[Category: Unreleased Structures]]
[[Category: Tassoni, R]]
[[Category: Ubbink, M]]
[[Category: Pannu, N.S]]

6h2i - Revision history

OCA at 15:59, 27 February 2019

OCA: Protected "6h2i" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6h2i is ON HOLD Authors: Tassoni, R., Pannu, N.S., Ubbink, M. Description: Structure of BlaC from Mycobacterium tuberculosis bound to the trans-ena...