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2g2u
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(New page: 200px<br /><applet load="2g2u" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g2u, resolution 1.60Å" /> '''Crystal Structure of...)
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Revision as of 08:47, 21 November 2007
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Crystal Structure of the SHV-1 Beta-lactamase/Beta-lactamase inhibitor protein (BLIP) complex
Overview
Beta-lactamase inhibitor protein (BLIP) binds a variety of class A, beta-lactamases with affinities ranging from micromolar to picomolar., Whereas the TEM-1 and SHV-1 beta-lactamases are almost structurally, identical, BLIP binds TEM-1 approximately 1000-fold tighter than SHV-1., Determining the underlying source of this affinity difference is important, for understanding the molecular basis of beta-lactamase inhibition and, mechanisms of protein-protein interface specificity and affinity. Here we, present the 1.6A resolution crystal structure of SHV-1.BLIP. In addition, a point mutation was identified, SHV D104E, that increases SHV.BLIP, binding affinity from micromolar to nanomolar. Comparison of the, SHV-1.BLIP structure with the published TEM-1.BLIP structure suggests that, the increased volume of Glu-104 stabilizes a key binding loop in the, interface. Solution of the 1.8A SHV D104K.BLIP crystal structure, identifies a novel conformation in which this binding loop is removed from, the interface. Using these structural data, we evaluated the ability of, EGAD, a program developed for computational protein design, to calculate, changes in the stability of mutant beta-lactamase.BLIP complexes. Changes, in binding affinity were calculated within an error of 1.6 kcal/mol of the, experimental values for 112 mutations at the TEM-1.BLIP interface and, within an error of 2.2 kcal/mol for 24 mutations at the SHV-1.BLIP, interface. The reasonable success of EGAD in predicting changes in, interface stability is a promising step toward understanding the stability, of the beta-lactamase.BLIP complexes and computationally assisted design, of tight binding BLIP variants.
About this Structure
2G2U is a Protein complex structure of sequences from Klebsiella pneumoniae and Streptomyces clavuligerus. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
Structural and computational characterization of the SHV-1 beta-lactamase-beta-lactamase inhibitor protein interface., Reynolds KA, Thomson JM, Corbett KD, Bethel CR, Berger JM, Kirsch JF, Bonomo RA, Handel TM, J Biol Chem. 2006 Sep 8;281(36):26745-53. Epub 2006 Jun 29. PMID:16809340
Page seeded by OCA on Wed Nov 21 10:55:12 2007
