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5x5g

From Proteopedia

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Current revision

Crystal structure of TLA-3 extended-spectrum beta-lactamase in a complex with OP0595

Structural highlights

5x5g is a 1 chain structure with sequence from Serratia marcescens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0B6VPP7_SERMA

Publication Abstract from PubMed

The development of effective inhibitors that block extended-spectrum beta-lactamases (ESBLs) and restore the action of beta-lactams represents an effective strategy against ESBL-producing Enterobacteriaceae We evaluated the inhibitory effects of the diazabicyclooctanes avibactam and OP0595 against TLA-3, an ESBL that we identified previously. Avibactam and OP0595 inhibited TLA-3 with apparent inhibitor constants (Kiapp) of 1.71 +/- 0.10 and 1.49 +/- 0.05 muM, respectively, and could restore susceptibility to cephalosporins in the TLA-3-producing Escherichia coli strain. The value of the second-order acylation rate constant (k2/K, where k2 is the acylation rate constant and K is the equilibrium constant) of avibactam [(3.25 +/- 0.03) x 10(3) M(-1) . s(-1)] was closer to that of class C and D beta-lactamases (k2/K, <10(4) M(-1) . s(-1)) than that of class A beta-lactamases (k2/K, >10(4) M(-1) . s(-1)). In addition, we determined the structure of TLA-3 and that of TLA-3 complexed with avibactam or OP0595 at resolutions of 1.6, 1.6, and 2.0 A, respectively. TLA-3 contains an inverted Omega loop and an extended loop between the beta5 and beta6 strands (insertion after Ser237), which appear only in PER-type class A beta-lactamases. These structures might favor the accommodation of cephalosporins harboring bulky R1 side chains. TLA-3 presented a high catalytic efficiency (kcat/Km ) against cephalosporins, including cephalothin, cefuroxime, and cefotaxime. Avibactam and OP0595 bound covalently to TLA-3 via the Ser70 residue and made contacts with residues Ser130, Thr235, and Ser237, which are conserved in ESBLs. Additionally, the sulfate group of the inhibitors formed polar contacts with amino acid residues in a positively charged pocket of TLA-3. Our findings provide a structural template for designing improved diazabicyclooctane-based inhibitors that are effective against ESBL-producing Enterobacteriaceae.

Structural Insights into the TLA-3 Extended-Spectrum beta-Lactamase and Its Inhibition by Avibactam and OP0595.,Jin W, Wachino JI, Yamaguchi Y, Kimura K, Kumar A, Yamada M, Morinaka A, Sakamaki Y, Yonezawa M, Kurosaki H, Arakawa Y Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: AAC.00501-17. doi:, 10.1128/AAC.00501-17. Print 2017 Oct. PMID:28739781^[1]

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

References

↑ Jin W, Wachino JI, Yamaguchi Y, Kimura K, Kumar A, Yamada M, Morinaka A, Sakamaki Y, Yonezawa M, Kurosaki H, Arakawa Y. Structural Insights into the TLA-3 Extended-Spectrum beta-Lactamase and Its Inhibition by Avibactam and OP0595. Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: AAC.00501-17. doi:, 10.1128/AAC.00501-17. Print 2017 Oct. PMID:28739781 doi:http://dx.doi.org/10.1128/AAC.00501-17

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/5x5g"

Categories: Large Structures | Serratia marcescens | Arakawa Y | Jin W | Wachino J

@@ Line 3: / Line 3: @@
 <StructureSection load='5x5g' size='340' side='right'caption='[[5x5g]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5x5g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X5G OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5X5G FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5x5g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X5G FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OP0:(2S,5R)-N-(2-AMINOETHOXY)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>OP0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OP0:(2S,5R)-N-(2-AMINOETHOXY)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>OP0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5x5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x5g OCA], [http://pdbe.org/5x5g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x5g RCSB], [http://www.ebi.ac.uk/pdbsum/5x5g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x5g 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=5x5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x5g OCA], [https://pdbe.org/5x5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x5g RCSB], [https://www.ebi.ac.uk/pdbsum/5x5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x5g ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A0B6VPP7_SERMA A0A0B6VPP7_SERMA]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Beta-lactamase]]
 [[Category: Large Structures]]
-[[Category: Arakawa, Y]]
+[[Category: Serratia marcescens]]
-[[Category: Jin, W]]
+[[Category: Arakawa Y]]
-[[Category: Wachino, J]]
+[[Category: Jin W]]
-[[Category: Extended-spectrum beta-lactamase]]
+[[Category: Wachino J]]
-[[Category: Hydrolase]]

5x5g

From Proteopedia

Current revision

Crystal structure of TLA-3 extended-spectrum beta-lactamase in a complex with OP0595

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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