NMR solution structure of the activation domain of human procarboxipeptidase A2

Activation domain of human procarboxipeptidase A2

Protein science : a publication of the Protein Society
NMR solution structure of the activation domain of human procarboxypeptidase A2.

A full-length cDNA clone coding for human pancreatic preprocarboxypeptidase A2
has been isolated from a lambda gt 11 human pancreatic library. Expression
clones were identified by specific interaction with antisera raised against the
native protein. The open reading frame of the polynucleotide sequence is 1254
base pairs in length and encodes a protein of 417 amino acids. This cDNA
includes a short leader signal peptide of 16 amino acids and a 94-amino
acid-long activation segment. The amino acid sequence shows 89% identity to
that of rat procarboxypeptidase A2, the only A2 form sequenced so far, and 64%
identity to that of human procarboxypeptidase A1. The newly determined sequence
was modeled to the three-dimensional crystal structures of both bovine
carboxypeptidase A and porcine procarboxypeptidase A1 by a novel distance
geometry approach. Biases in the modeling were avoided by relying exclusively
on automatic procedures and by using random structures as starting points.
Information taken from the known homologous structures refers only to the
backbone since no explicit data describing the conformation of side chains were
transferred. Ten structures of human carboxypeptidase A2 were determined on the
basis of each of the two known crystal structures. The root-mean-square
distance for the backbone atoms between the 10 structures and their mean for
237 selected residues is 0.7 A when starting from the bovine protein and 0.8 A
for 251 selected residues when starting from the porcine protein. The 94
residue-long activation segment was also determined in the modeling based on
the porcine zymogen; its structure is well defined but not its orientation with
respect to the enzyme moiety. The model obtained for human procarboxypeptidase
A2 is discussed with respect to the specificity and activation of the enzyme.

Catasus Ll, Vendrell J, Aviles FX,
Carreira S, Puigserver & Billeter M.
The sequence and conformation of human
pancratic procarboxipeptidase A2.
cDNA cloning, sequence analysis,
and 3D model.
J. Biol. Chem. 270, 6651-6657 (1995).

The sequence and conformation of human pancreatic procarboxypeptidase A2. cDNA cloning, sequence analysis, and three-dimensional model.

Activation domain of human procarboxipeptidase

preprocarboxypeptidase A2 [Homo sapiens]

Carboxypeptidase A2 (pancreatic) [Homo sapiens]

carboxypeptidase A2 precursor [Homo sapiens]

PREDICTED: carboxypeptidase A2 [Pan troglodytes]

PREDICTED: LOW QUALITY PROTEIN: carboxypeptidase A2 [Pongo abelii]

PREDICTED: carboxypeptidase A2 [Pan paniscus]

RecName: Full=Carboxypeptidase A2; Flags: Precursor [Homo sapiens]