4id4: Difference between revisions
New page: '''Unreleased structure''' The entry 4id4 is ON HOLD Authors: Park, J., Gobeil, S., Pelletier, J.N., Berghuis, A.M. Description: Crystal structure of chimeric beta-lactamase cTEM-17m |
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The | ==Crystal structure of chimeric beta-lactamase cTEM-17m== | ||
<StructureSection load='4id4' size='340' side='right'caption='[[4id4]], [[Resolution|resolution]] 1.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4id4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ID4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ID4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.05Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4id4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4id4 OCA], [https://pdbe.org/4id4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4id4 RCSB], [https://www.ebi.ac.uk/pdbsum/4id4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4id4 ProSAT]</span></td></tr> | |||
</table> | |||
== 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.[https://www.uniprot.org/uniprot/BLP4_PSEAI BLP4_PSEAI] Hydrolyzes both carbenicillin and oxacillin. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Proteins are dynamic systems, and understanding dynamics is critical for fully understanding protein function. Therefore, the question of whether laboratory engineering has an impact on protein dynamics is of general interest. Here, we demonstrate that two homologous, naturally evolved enzymes with high degrees of structural and functional conservation also exhibit conserved dynamics. Their similar set of slow timescale dynamics is highly restricted, consistent with evolutionary conservation of a functionally important feature. However, we also show that dynamics of a laboratory-engineered chimeric enzyme obtained by recombination of the two homologs exhibits striking difference on the millisecond timescale, despite function and high-resolution crystal structure (1.05 A) being conserved. The laboratory-engineered chimera is thus functionally tolerant to modified dynamics on the timescale of catalytic turnover. Tolerance to dynamic variation implies that maintenance of native-like protein dynamics may not be required when engineering functional proteins. | |||
Maintenance of Native-like Protein Dynamics May Not Be Required for Engineering Functional Proteins.,Gobeil SM, Clouthier CM, Park J, Gagne D, Berghuis AM, Doucet N, Pelletier JN Chem Biol. 2014 Sep 3. pii: S1074-5521(14)00248-8. doi:, 10.1016/j.chembiol.2014.07.016. PMID:25200606<ref>PMID:25200606</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4id4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa]] | |||
[[Category: Berghuis AM]] | |||
[[Category: Gobeil S]] | |||
[[Category: Park J]] | |||
[[Category: Pelletier JN]] | |||
Latest revision as of 18:20, 20 September 2023
Crystal structure of chimeric beta-lactamase cTEM-17mCrystal structure of chimeric beta-lactamase cTEM-17m
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.BLP4_PSEAI Hydrolyzes both carbenicillin and oxacillin. Publication Abstract from PubMedProteins are dynamic systems, and understanding dynamics is critical for fully understanding protein function. Therefore, the question of whether laboratory engineering has an impact on protein dynamics is of general interest. Here, we demonstrate that two homologous, naturally evolved enzymes with high degrees of structural and functional conservation also exhibit conserved dynamics. Their similar set of slow timescale dynamics is highly restricted, consistent with evolutionary conservation of a functionally important feature. However, we also show that dynamics of a laboratory-engineered chimeric enzyme obtained by recombination of the two homologs exhibits striking difference on the millisecond timescale, despite function and high-resolution crystal structure (1.05 A) being conserved. The laboratory-engineered chimera is thus functionally tolerant to modified dynamics on the timescale of catalytic turnover. Tolerance to dynamic variation implies that maintenance of native-like protein dynamics may not be required when engineering functional proteins. Maintenance of Native-like Protein Dynamics May Not Be Required for Engineering Functional Proteins.,Gobeil SM, Clouthier CM, Park J, Gagne D, Berghuis AM, Doucet N, Pelletier JN Chem Biol. 2014 Sep 3. pii: S1074-5521(14)00248-8. doi:, 10.1016/j.chembiol.2014.07.016. PMID:25200606[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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