Comparisons of the three-dimensional structures, specificities and glycosylation of renins, yeast proteinase A and cathepsin D.
The crystal structures of complexes of the aspartic proteinases, human and mouse renins, yeast proteinase A and cathepsin D, with peptide analogue inhibitors are compared. Differences occur in the relative positions of the domain comprising residues 190-302 (pepsin numbering) compared to the remaining structure and in the nature and position of the irregular regions joining the beta-strands and alpha-helices. The first three of the five residues of the oligosaccharide structures attached to Asn 67 of yeast proteinase and cathepsin D cover the same region of the protein surface. All enzymes have an unusual, proline-rich region (292-297) which acts as a second flap (in addition to that involving residues 72-81). This covers the active site cleft, but can be very close to the substrate/inhibitor at P3' and P4' only in the renins.
Department of Crystallography, Birkbeck College, London, UK.
C F
CF
Aguilar
V
V
Dhanaraj
K
K
Guruprasad
C
C
Dealwis
M
M
Badasso
J B
JB
Cooper
S P
SP
Wood
T L
TL
Blundell
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002402:Cathepsin D / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D018360:Crystallography, X-Ray; D006031:Glycosylation; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification; D010802:Phylogeny; D011480:Protease Inhibitors / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012083:Renin / Q000737:chemistry* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D009842:Oligopeptides; D009844:Oligosaccharides; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D012083:Renin; C022442:aspergillopepsin II; D002402:Cathepsin D