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4x69

From Proteopedia

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Current revision

Crystal structure of OP0595 complexed with CTX-M-44

Structural highlights

4x69 is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.42Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BLT1_ECOLX Has strong cefotaxime-hydrolyzing activity.

Publication Abstract from PubMed

OBJECTIVES: The production of a growing diversity of beta-lactamases by Gram-negative bacteria challenges antimicrobial chemotherapy. OP0595, discovered separately by each of Meiji Seika Pharma and Fedora Pharmaceuticals, is a new diazabicyclooctane serine beta-lactamase inhibitor that also acts as an antibiotic and as a beta-lactamase-independent beta-lactam 'enhancer'. METHODS: Inhibitory activity against serine beta-lactamases and affinity for PBPs were determined using nitrocefin and Bocillin FL, respectively. MICs alone and in combination with beta-lactam agents were measured according to CLSI recommendations. Morphological changes in Escherichia coli were examined by phase-contrast microscopy. RESULTS: IC50s of OP0595 for class A and C beta-lactamases were <1000 nM, with covalent binding demonstrated to the active-site serine of CTX-M-44 and AmpC enzymes. OP0595 also had direct antibiotic activity against many Enterobacteriaceae, associated with inhibition of PBP2 and conversion of the bacteria into spherical forms. Synergy between OP0595 and beta-lactam agents was seen against strains producing class A and C beta-lactamases vulnerable to inhibition. Lastly, OP0595 lowered the MICs of PBP3-targeted partner beta-lactam agents for a non-beta-lactamase-producing E. coli mutant that was resistant to OP0595 itself, indicating beta-lactamase-independent 'enhancer'-based synergy. CONCLUSIONS: OP0595 acts in three ways: (i) as an inhibitor of class A and C beta-lactamases, covalently binding at their active sites; (ii) as an antibacterial, by inhibiting PBP2 of several Enterobacteriaceae; and (iii) as an 'enhancer' of beta-lactam agents that bind to other PBPs besides PBP2 for several Enterobacteriaceae. OP0595 has considerable potential to overcome resistance when it is combined with various beta-lactam agents.

OP0595, a new diazabicyclooctane: mode of action as a serine beta-lactamase inhibitor, antibiotic and beta-lactam 'enhancer'.,Morinaka A, Tsutsumi Y, Yamada M, Suzuki K, Watanabe T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Mitsuhashi N, Ida T, Livermore DM J Antimicrob Chemother. 2015 Jun 18. pii: dkv166. PMID:26089439^[1]

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

References

↑ Morinaka A, Tsutsumi Y, Yamada M, Suzuki K, Watanabe T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Mitsuhashi N, Ida T, Livermore DM. OP0595, a new diazabicyclooctane: mode of action as a serine beta-lactamase inhibitor, antibiotic and beta-lactam 'enhancer'. J Antimicrob Chemother. 2015 Jun 18. pii: dkv166. PMID:26089439 doi:http://dx.doi.org/10.1093/jac/dkv166

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4x69"

Categories: Escherichia coli | Large Structures | Watanabe T | Yamada M

@@ Line 1: / Line 1: @@
 ==Crystal structure of OP0595 complexed with CTX-M-44==
-<StructureSection load='4x69' size='340' side='right' caption='[[4x69]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
+<StructureSection load='4x69' size='340' side='right'caption='[[4x69]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x69]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X69 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x69]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X69 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OP0:(2S,5R)-N-(2-AMINOETHOXY)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>OP0</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]] 1.42&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x68|4x68]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OP0:(2S,5R)-N-(2-AMINOETHOXY)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>OP0</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4x69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x69 OCA], [https://pdbe.org/4x69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x69 RCSB], [https://www.ebi.ac.uk/pdbsum/4x69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x69 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=4x69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x69 OCA], [http://pdbe.org/4x69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x69 RCSB], [http://www.ebi.ac.uk/pdbsum/4x69 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/BLT1_ECOLX BLT1_ECOLX]] Has strong cefotaxime-hydrolyzing activity.
+[https://www.uniprot.org/uniprot/BLT1_ECOLX BLT1_ECOLX] Has strong cefotaxime-hydrolyzing activity.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 4x69" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Beta-lactamase]]
+[[Category: Escherichia coli]]
-[[Category: Watanabe, T]]
+[[Category: Large Structures]]
-[[Category: Yamada, M]]
+[[Category: Watanabe T]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Yamada M]]

4x69

From Proteopedia

Current revision

Crystal structure of OP0595 complexed with CTX-M-44

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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