2g2u | pdb_00002g2u

Crystal Structure of the SHV-1 Beta-lactamase/Beta-lactamase inhibitor protein (BLIP) complex

spinqualitylabelsall models 2g2u, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2g2u is a 2 chain structure with sequence from "bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886 and As 4.1611. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 2g2w Gene: bla, shv1 ("Bacillus pneumoniae" (Schroeter 1886) Flugge 1886) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [BLIP_STRCL] Inhibits a wide variety of beta lactamases. 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 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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