3n4i

Crystal structure of the SHV-1 D104E beta-lactamase/beta-lactamase inhibitor protein (BLIP) complex

spinqualitylabelsall models 3n4i, resolution 1.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n4i is a 2 chain structure with sequence from Klebsiella pneumoniae and Streptomyces clavuligerus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.56Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLA1_KLEPN Publication Abstract from PubMed Establishing a quantitative understanding of the determinants of affinity in protein-protein interactions remains challenging. For example, TEM-1/beta-lactamase inhibitor protein (BLIP) and SHV-1/BLIP are homologous beta-lactamase/beta-lactamase inhibitor protein complexes with disparate K(d) values (3 nM and 2 muM, respectively), and a single substitution, D104E in SHV-1, results in a 1000-fold enhancement in binding affinity. In TEM-1, E104 participates in a salt bridge with BLIP K74, whereas the corresponding SHV-1 D104 does not in the wild type SHV-1/BLIP co-structure. Here, we present a 1.6 A crystal structure of the SHV-1 D104E/BLIP complex that demonstrates that this point mutation restores this salt bridge. Additionally, mutation of a neighboring residue, BLIP E73M, results in salt bridge formation between SHV-1 D104 and BLIP K74 and a 400-fold increase in binding affinity. To understand how this salt bridge contributes to complex affinity, the cooperativity between the E/K or D/K salt bridge pair and a neighboring hot spot residue (BLIP F142) was investigated using double mutant cycle analyses in the background of the E73M mutation. We find that BLIP F142 cooperatively stabilizes both interactions, illustrating how a single mutation at a hot spot position can drive large perturbations in interface stability and specificity through a cooperative interaction network. Proteins 2011. (c) 2011 Wiley-Liss, Inc. Specificity and cooperativity at beta-lactamase position 104 in TEM-1/BLIP and SHV-1/BLIP interactions.,Hanes MS, Reynolds KA, McNamara C, Ghosh P, Bonomo RA, Kirsch JF, Handel TM Proteins. 2010 Dec 13. doi: 10.1002/prot.22961. PMID:21294157 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures TEM1-beta-Lactamase/beta-lactamase Inhibitor Protein (BLIP)

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