Structural highlights
3e2l is a 4 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.
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| NonStd Res: | |
| Related: | 2ov5, 1jtg, 2g2u, 3e2k |
| Gene: | KPC-2, blaKPC-2 ("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
KPC beta-lactamases hydrolyze the "last resort" beta-lactam antibiotics (carbapenems) used to treat multidrug resistant infections and are compromising efforts to combat life-threatening Gram-negative bacterial infections in hospitals worldwide. Consequently, the development of novel inhibitors is essential for restoring the effectiveness of existing antibiotics. The beta-lactamase inhibitor protein (BLIP) is a competitive inhibitor of a number of class A beta-lactamases. In this study, we characterize the previously unreported interaction between KPC-2 beta-lactamase and BLIP. Biochemical results show that BLIP is an extremely potent inhibitor of KPC enzymes, binding KPC-2 and KPC-3 with subnanomolar affinity. To understand the basis of affinity and specificity in the beta-lactamase-BLIP system, the crystallographic structure of the KPC-2-BLIP complex was determined to 1.9 A resolution. Computational alanine scanning was also conducted to identify putative hot spots in the KPC-2-BLIP interface. Interestingly, the two complexes making up the KPC-2-BLIP asymmetric unit are distinct, and in one structure, the BLIP F142 loop is absent, in contrast to homologous structures in which it occupies the active site. This finding and other sources of structural plasticity appear to contribute to BLIP's promiscuity, enabling it to respond to mutations at the beta-lactamase interface. Given the continuing emergence of antibiotic resistance, the high-resolution KPC-2-BLIP structure will facilitate its use as a template for the rational design of new inhibitors of this problematic enzyme.
Structural and biochemical characterization of the interaction between KPC-2 beta-lactamase and beta-lactamase inhibitor protein .,Hanes MS, Jude KM, Berger JM, Bonomo RA, Handel TM Biochemistry. 2009 Oct 6;48(39):9185-93. PMID:19731932[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hanes MS, Jude KM, Berger JM, Bonomo RA, Handel TM. Structural and biochemical characterization of the interaction between KPC-2 beta-lactamase and beta-lactamase inhibitor protein . Biochemistry. 2009 Oct 6;48(39):9185-93. PMID:19731932 doi:10.1021/bi9007963
