Inhibitor binding induces structural changes in porcine pepsin.
The refined structures of two isomorphous pepsin/inhibitor complexes demonstrate that significant conformational changes take place upon ligand binding for a mammalian representative of the aspartic proteinase family. These differences can be attributed mostly to the concerted rigid body movements of two separate clusters of residues relative to a central core. One cluster in the amino domain comprises the flap, the adjacent beta strand (sheet IV) and helices, as well as the interconnecting loops. The other, larger cluster is in the carboxy end and corresponds approximately to the flexible subdomain described previously. Similar conformational changes are proposed to occur in renin and cathepsin D.
Abad-Zapatero
C
C
Laboratory of Protein Crystallography, Abbott Laboratories, Abbott Park, Illinois 60064.
Rydel
T J
TJ
Neidhart
D J
DJ
Luly
J
J
Erickson
J W
JW
D000818:Animals; D001665:Binding Sites; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D010434:Pepsin A / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011487:Protein Conformation; D013552:Swine
D010434:Pepsin A