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| | <StructureSection load='1ong' size='340' side='right'caption='[[1ong]], [[Resolution|resolution]] 1.10Å' scene=''> | | <StructureSection load='1ong' size='340' side='right'caption='[[1ong]], [[Resolution|resolution]] 1.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ong]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ONG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ONG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ong]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ONG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ONG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=WY4:7-(5,6-DIHYDRO-8H-IMIDAZO[2,1-C][1,4]OXAZIN-2-YL)-6-FORMYL-2,7-DIHYDRO-+[1,4]THIAZEPINE-3-CARBOXYLIC+ACID'>WY4</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]] 1.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1shv|1shv]], [[1g56|1g56]], [[1onh|1onh]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=WY4:7-(5,6-DIHYDRO-8H-IMIDAZO[2,1-C][1,4]OXAZIN-2-YL)-6-FORMYL-2,7-DIHYDRO-+[1,4]THIAZEPINE-3-CARBOXYLIC+ACID'>WY4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BLA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1ong FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ong OCA], [https://pdbe.org/1ong PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ong RCSB], [https://www.ebi.ac.uk/pdbsum/1ong PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ong ProSAT]</span></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=1ong FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ong OCA], [https://pdbe.org/1ong PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ong RCSB], [https://www.ebi.ac.uk/pdbsum/1ong PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ong ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BLA1_KLEPN BLA1_KLEPN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bonomo, R A]] | + | [[Category: Bonomo RA]] |
| - | [[Category: Knox, J R]] | + | [[Category: Knox JR]] |
| - | [[Category: Mayama, K]] | + | [[Category: Mayama K]] |
| - | [[Category: Nukaga, M]] | + | [[Category: Nukaga M]] |
| - | [[Category: Beta-lactam hydrolase]]
| + | |
| - | [[Category: Detergent binding]]
| + | |
| - | [[Category: Drug design]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Penicillinase]]
| + | |
| Structural highlights
Function
BLA1_KLEPN
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A new beta-lactamase inhibitor, a methylidene penem having a 5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine heterocyclic substituent at the C6 position with a Z configuration, irreversibly inhibits both class A and class C serine beta-lactamases with IC(50) values of 0.4 and 9.0 nM for TEM-1 and SHV-1 (class A), respectively, and 4.8 nM in AmpC (class C) beta-lactamases. The compound also inhibits irreversibly the class C extended-spectrum GC1 beta-lactamase (IC(50) = 6.2 nM). High-resolution crystallographic structures of a reaction intermediate of (5R)-(6Z)-6-(5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazin-2-ylmethylene)-7-oxo -4-thia-1-azabicyclo[3.2.0]hept-2-ene-3-carboxylic acid 1 with the SHV-1 beta-lactamase and with the GC1 beta-lactamase have been determined by X-ray diffraction to resolutions of 1.10 and 1.38 A, respectively. The two complexes were refined to crystallographic R-factors (R(free)) of 0.141 (0.186) and 0.138 (0.202), respectively. Cryoquenching of the reaction of 1 with each beta-lactamase crystal produced a common, covalently bound intermediate. After acylation of the serine, a nucleophilic attack by the departing thiolate on the C6' atom yielded a novel seven-membered 1,4-thiazepine ring having R stereochemistry at the new C7 moiety. The orientation of this ring in each complex differs by a 180 degrees rotation about the bond to the acylated serine. The acyl ester bond is stabilized to hydrolysis through resonance stabilization with the dihydrothiazepine ring and by low occupancy or disorder of hydrolytic water molecules. In the class A complex, the buried water molecule on the alpha-face of the ester bond appears to be loosely bound or absent. In the class C complex, a water molecule on the beta-face is disordered and poorly activated for hydrolysis. Here, the acyl intermediate is unable to assist its own hydrolysis, as is thought to occur with many class C substrates.
Inhibition of class A and class C beta-lactamases by penems: crystallographic structures of a novel 1,4-thiazepine intermediate.,Nukaga M, Abe T, Venkatesan AM, Mansour TS, Bonomo RA, Knox JR Biochemistry. 2003 Nov 18;42(45):13152-9. PMID:14609325[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nukaga M, Abe T, Venkatesan AM, Mansour TS, Bonomo RA, Knox JR. Inhibition of class A and class C beta-lactamases by penems: crystallographic structures of a novel 1,4-thiazepine intermediate. Biochemistry. 2003 Nov 18;42(45):13152-9. PMID:14609325 doi:10.1021/bi034986b
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