'''Crystal Structure of the SHV D104K Beta-lactamase/Beta-lactamase inhibitor protein (BLIP) complex'''
===Crystal Structure of the SHV D104K 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.
The line below this paragraph, {{ABSTRACT_PUBMED_16809340}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 16809340 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_16809340}}
==About this Structure==
==About this Structure==
Line 37:
Line 41:
[[Category: Protein-protein complex]]
[[Category: Protein-protein complex]]
[[Category: Shv]]
[[Category: Shv]]
''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 Mon Jul 28 02:55:17 2008''
Revision as of 23:55, 27 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
