Zinc carboxypeptidase explained
The carboxypeptidase A family can be divided into two subfamilies: carboxypeptidase H (regulatory) and carboxypeptidase A (digestive).[1] Members of the H family have longer C-termini than those of family A,[2] and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble.
The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif.[1] [3] Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended alpha-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts.[4]
Other examples of protein families in this entry include:
- Intron maturase
- Putative mitochondrial processing peptidase alpha subunit
- Superoxide dismutase [Mn]
- Asparagine synthetase [glutamine-hydrolysing] 3
- Glucose-6-phosphate isomerase
Human proteins containing this domain
AEBP1
- AGBL1; AGBL2; AGBL3; AGBL4; AGBL5; AGTPBP1; CPA1; CPA2
CPA3; CPA4; CPA5; CPA6; CPB1; CPB2; CPD; CPE
CPM; CPN1; CPO; CPXM1; CPXM2; CPZ;
Notes and References
- Book: Rawlings ND, Barrett AJ . Evolutionary families of metallopeptidases . Meth. Enzymol. . 248 . 183–228 . 1995 . 7674922 . 10.1016/0076-6879(95)48015-3. 978-0-12-182149-4 .
- Osterman AL, Grishin NV, Smulevitch SV, Zagnitko OP, Matz MV, Stepanov VM, Revina LP . Primary structure of carboxypeptidase T: delineation of functionally relevant features in Zn-carboxypeptidase family . J. Protein Chem. . 11 . 5 . 561–570 . 1992 . 1449602 . 10.1007/bf01025034. 22920252 .
- Lipscomb WN, Rees DC, Lewis M . Refined crystal structure of carboxypeptidase A at 1.54 A resolution . J. Mol. Biol. . 168 . 2 . 367–387 . 1983 . 6887246 . 10.1016/S0022-2836(83)80024-2.
- Huber R, Guasch A, Coll M, Aviles FX . Three-dimensional structure of porcine pancreatic procarboxypeptidase A. A comparison of the A and B zymogens and their determinants for inhibition and activation . J. Mol. Biol. . 224 . 1 . 141–157 . 1992 . 1548696 . 10.1016/0022-2836(92)90581-4.
