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2g2u
From Proteopedia
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| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | bla, shv1 (Klebsiella pneumoniae) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Related: | 2G2W
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Mon Mar 31 03:11:02 2008
