Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin.
The crystal structure of an activation intermediate of human gastricsin has been determined at 2.4 A resolution. The human digestive enzyme gastricsin (pepsin C) is an aspartic proteinase that is synthesized as the inactive precursor (zymogen) progastricsin (pepsinogen C or hPGC). In the zymogen, a positively-charged N-terminal prosegment of 43 residues (Ala 1p-Leu 43p; the suffix 'p' refers to the prosegment) sterically prevents the approach of a substrate to the active site. Zymogen conversion occurs in an autocatalytic and stepwise fashion at low pH through the formation of intermediates. The structure of the non-covalent complex of a partially-cleaved peptide of the prosegment (Ala 1p-Phe 26p) with mature gastricsin (Ser 1-Ala 329) suggests an activation pathway that may be common to all gastric aspartic proteinases.
Khan
A R
AR
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Cherney
M M
MM
Tarasova
N I
NI
James
M N
MN
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
D004792:Enzyme Precursors; D010434:Pepsin A; C020557:gastricsin