Astacin

Astacin
structure of astacin with a hydroxamic acid inhibitor
Identifiers
SymbolAstacin
PfamPF01400
Pfam clanCL0126
InterProIPR001506
PROSITEPDOC00129
MEROPSM12
SCOP21ast / SCOPe / SUPFAM
CDDcd04280
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
astacin
Identifiers
EC no.3.4.24.21
CAS no.143179-21-9
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Astacins are a family of multidomain metalloendopeptidases which are either secreted or membrane-anchored.[1] These metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A (astacin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH.[2]

The astacin family of metalloendopeptidases (EC 3.4.24.21) encompasses a range of proteins found in hydra to humans, in mature and developmental systems.[3] Their functions include activation of growth factors, degradation of polypeptides, and processing of extracellular proteins.[3] The proteins are synthesised with N-terminal signal and pro-enzyme sequences, and many contain multiple domains C-terminal to the protease domain. They are either secreted from cells, or are associated with the plasma membrane.

The astacin molecule adopts a kidney shape, with a deep active-site cleft between its N- and C-terminal domains.[4] The zinc ion, which lies at the bottom of the cleft, exhibits a unique penta-coordinated mode of binding, involving 3 histidine residues, a tyrosine and a water molecule (which is also bound to the carboxylate side chain of Glu93).[4] The N-terminal domain comprises 2 alpha-helices and a 5-stranded beta-sheet. The overall topology of this domain is shared by the archetypal zinc-endopeptidase thermolysin. Astacin protease domains also share common features with serralysins, matrix metalloendopeptidases, and snake venom proteases; they cleave peptide bonds in polypeptides such as insulin B chain and bradykinin, and in proteins such as casein and gelatin; and they have arylamidase activity.[3]

  1. ^ Gomis-Rüth FX, Trillo-Muyo S, Stöcker W (October 2012). "Functional and structural insights into astacin metallopeptidases". Biological Chemistry. 393 (10): 1027–41. doi:10.1515/hsz-2012-0149. hdl:10261/87872. PMID 23092796. S2CID 11098025.
  2. ^ Rawlings ND, Barrett AJ (1995). "Evolutionary families of metallopeptidases". Proteolytic Enzymes: Aspartic and Metallo Peptidases. Methods in Enzymology. Vol. 248. pp. 183–228. doi:10.1016/0076-6879(95)48015-3. ISBN 9780121821494. PMID 7674922.
  3. ^ a b c Bond JS, Beynon RJ (July 1995). "The astacin family of metalloendopeptidases". Protein Science. 4 (7): 1247–61. doi:10.1002/pro.5560040701. PMC 2143163. PMID 7670368.
  4. ^ a b Gomis-Rüth FX, Stöcker W, Huber R, Zwilling R, Bode W (February 1993). "Refined 1.8 A X-ray crystal structure of astacin, a zinc-endopeptidase from the crayfish Astacus astacus L. Structure determination, refinement, molecular structure and comparison with thermolysin". Journal of Molecular Biology. 229 (4): 945–68. doi:10.1006/jmbi.1993.1098. PMID 8445658.