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Isotope-edited proton NMR study on the structure of a pepsin/inhibitor complex

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00422a001· OSTI ID:6142267
A general approach is illustrated for providing detailed structural information on large enzyme/inhibitor complexes using NMR spectroscopy. The method involves the use of isotopically labeled ligands to simplify two-dimensional NOE spectra of large molecular complexes by isotope-editing techniques. With this approach, the backbone and side-chain conformations (at the P/sub 2/ and P/sub 3/ sites) of a tightly bound inhibitor of porcine pepsin have bene determined. In addition, structural information on the active site of pepsin has been obtained. Due to the sequence homology between porcine pepsin and human renin, this structural information may prove useful for modeling renin/inhibitor complexes with the ultimate goal of designing more effective renin inhibitors. Moreover, this general approach can be applied to study other biological systems of interest such as other enzyme/inhibitor complexes, ligands bound to soluble receptors, and enzyme/substrate interactions.
Research Organization:
Abbott Labs., Abbott Park, IL (USA)
OSTI ID:
6142267
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:22; ISSN BICHA
Country of Publication:
United States
Language:
English