1htz

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{{STRUCTURE_1htz| PDB=1htz | SCENE= }}
{{STRUCTURE_1htz| PDB=1htz | SCENE= }}
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'''CRYSTAL STRUCTURE OF TEM52 BETA-LACTAMASE'''
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===CRYSTAL STRUCTURE OF TEM52 BETA-LACTAMASE===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 11224569 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11224569}}
==About this Structure==
==About this Structure==
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[[Category: Stevens, R C.]]
[[Category: Stevens, R C.]]
[[Category: Mutant form of beta-lactamase]]
[[Category: Mutant form of beta-lactamase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:13:44 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:40:29 2008''

Revision as of 05:40, 1 July 2008

Image:1htz.png

Template:STRUCTURE 1htz

CRYSTAL STRUCTURE OF TEM52 BETA-LACTAMASE

Template:ABSTRACT PUBMED 11224569

About this Structure

1HTZ is a Single protein structure of sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA.

Reference

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

Page seeded by OCA on Tue Jul 1 08:40:29 2008

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