|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1htz' size='340' side='right'caption='[[1htz]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1htz' size='340' side='right'caption='[[1htz]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1htz]] is a 6 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=1HTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HTZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1htz]] is a 6 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=1HTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HTZ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1tem|1tem]]</div></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]] 2.4Å</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=1htz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1htz OCA], [https://pdbe.org/1htz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1htz RCSB], [https://www.ebi.ac.uk/pdbsum/1htz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1htz 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=1htz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1htz OCA], [https://pdbe.org/1htz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1htz RCSB], [https://www.ebi.ac.uk/pdbsum/1htz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1htz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q9R435_KLEPN Q9R435_KLEPN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 34: |
Line 35: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Orencia, M C]] | + | [[Category: Orencia MC]] |
| - | [[Category: Stevens, R C]] | + | [[Category: Stevens RC]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mutant form of beta-lactamase]]
| + | |
| Structural highlights
Function
Q9R435_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
Directed evolution can be a powerful tool to predict antibiotic resistance. Resistance involves the accumulation of mutations beneficial to the pathogen while maintaining residue interactions and core packing that are critical for preserving function. The constraint of maintaining stability, while increasing activity, drastically reduces the number of possible mutational combination pathways. To test this theory, TEM-1 beta-lactamase was evolved using a hypermutator E. coli-based directed evolution technique with cefotaxime selection. The selected mutants were compared to two previous directed evolution studies and a database of clinical isolates. In all cases, evolution resulted in the generation of the E104K/M182T/G238S combination of mutations ( approximately 500-fold increased resistance), which is equivalent to clinical isolate TEM-52. The structure of TEM-52 was determined to 2.4 A. G238S widens access to the active site by 2.8 A whereas E104K stabilizes the reorganized topology. The M182T mutation is located 17 A from the active site and appears to be a global suppressor mutation that acts to stabilize the new enzyme structure. Our results demonstrate that directed evolution coupled with structural analysis can be used to predict future mutations that lead to increased antibiotic resistance.
Predicting the emergence of antibiotic resistance by directed evolution and structural analysis.,Orencia MC, Yoon JS, Ness JE, Stemmer WP, Stevens RC Nat Struct Biol. 2001 Mar;8(3):238-42. PMID:11224569[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Orencia MC, Yoon JS, Ness JE, Stemmer WP, Stevens RC. Predicting the emergence of antibiotic resistance by directed evolution and structural analysis. Nat Struct Biol. 2001 Mar;8(3):238-42. PMID:11224569 doi:10.1038/84981
|
