2g2u
From Proteopedia
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| - | + | {{STRUCTURE_2g2u| PDB=2g2u | SCENE= }} | |
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'''Crystal Structure of the SHV-1 Beta-lactamase/Beta-lactamase inhibitor protein (BLIP) complex''' | '''Crystal Structure of the SHV-1 Beta-lactamase/Beta-lactamase inhibitor protein (BLIP) complex''' | ||
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[[Category: Reynolds, K A.]] | [[Category: Reynolds, K A.]] | ||
[[Category: Thomson, J M.]] | [[Category: Thomson, J M.]] | ||
| - | [[Category: | + | [[Category: Beta-lactamase]] |
| - | [[Category: | + | [[Category: Beta-lactamase inhibitor]] |
| - | [[Category: | + | [[Category: Blip]] |
| - | [[Category: | + | [[Category: Protein-protein complex]] |
| - | [[Category: | + | [[Category: Shv-1]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:37:36 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 01:37, 4 May 2008
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. 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 Sun May 4 04:37:36 2008
