4zj2: Difference between revisions
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==Crystal Structure of p-acrylamido-phenylalanine modified TEM1 beta-lactamase from Escherichia coli :E166N mutant== | ==Crystal Structure of p-acrylamido-phenylalanine modified TEM1 beta-lactamase from Escherichia coli :E166N mutant== | ||
<StructureSection load='4zj2' size='340' side='right' caption='[[4zj2]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='4zj2' size='340' side='right'caption='[[4zj2]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4zj2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJ2 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4zj2]] is a 1 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=4ZJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZJ2 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OV:(2R)-2-[(1R)-2-[(2S)-2-AMINO-2-CARBOXYETHOXY]-1-{[(2R)-2-AMINO-2-PHENYLACETYL]AMINO}-2-OXOETHYL]-5-METHYL-3,6-DIHYDRO-2H-1,3-THIAZINE-4-CARBOXYLIC+ACID'>4OV</scene></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=4zj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zj2 OCA], [https://pdbe.org/4zj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zj2 RCSB], [https://www.ebi.ac.uk/pdbsum/4zj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zj2 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/BLAT_ECOLX BLAT_ECOLX] TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 4zj2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4zj2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: Choi | [[Category: Large Structures]] | ||
[[Category: Han | [[Category: Choi S]] | ||
[[Category: Nasertorabi | [[Category: Han GW]] | ||
[[Category: Reed | [[Category: Nasertorabi F]] | ||
[[Category: Schultz | [[Category: Reed SA]] | ||
[[Category: Stevens | [[Category: Schultz PG]] | ||
[[Category: Xiao | [[Category: Stevens CS]] | ||
[[Category: Xiao H]] | |||
Latest revision as of 11:18, 27 September 2023
Crystal Structure of p-acrylamido-phenylalanine modified TEM1 beta-lactamase from Escherichia coli :E166N mutantCrystal Structure of p-acrylamido-phenylalanine modified TEM1 beta-lactamase from Escherichia coli :E166N mutant
Structural highlights
FunctionBLAT_ECOLX TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors. Publication Abstract from PubMedWith few exceptions, all living organisms encode the same 20 canonical amino acids; however, it remains an open question whether organisms with additional amino acids beyond the common 20 might have an evolutionary advantage. Here, we begin to test that notion by making a large library of mutant enzymes in which 10 structurally distinct noncanonical amino acids were substituted at single sites randomly throughout TEM-1 beta-lactamase. A screen for growth on the beta-lactam antibiotic cephalexin afforded a unique p-acrylamido-phenylalanine (AcrF) mutation at Val-216 that leads to an increase in catalytic efficiency by increasing kcat, but not significantly affecting KM. To understand the structural basis for this enhanced activity, we solved the X-ray crystal structures of the ligand-free mutant enzyme and of the deacylation-defective wild-type and mutant cephalexin acyl-enzyme intermediates. These structures show that the Val-216-AcrF mutation leads to conformational changes in key active site residues-both in the free enzyme and upon formation of the acyl-enzyme intermediate-that lower the free energy of activation of the substrate transacylation reaction. The functional changes induced by this mutation could not be reproduced by substitution of any of the 20 canonical amino acids for Val-216, indicating that an expanded genetic code may offer novel solutions to proteins as they evolve new activities. Exploring the potential impact of an expanded genetic code on protein function.,Xiao H, Nasertorabi F, Choi SH, Han GW, Reed SA, Stevens RC, Schultz PG Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6961-6. doi:, 10.1073/pnas.1507741112. Epub 2015 May 18. PMID:26038548[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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