2CKI

Structure of Ulilysin, a member of the pappalysin family of metzincin metalloendopeptidases.

Summary for 2CKI

• Entry DOI: 10.2210/pdb2cki/pdb
• Descriptor: ULILYSIN, ARGININE, VALINE, ... (7 entities in total)
• Functional Keywords: metalloprotease, hydrolase
• Biological source: METHANOSARCINA ACETIVORANS
• Total number of polymer chains: 2
• Total formula weight: 60035.35

Authors

Tallant, C.,Garcia-Castellanos, R.,Seco, J.,Baumann, U.,Gomis-Ruth, F.X. (deposition date: 2006-04-19, release date: 2006-05-09, Last modification date: 2019-05-08)

Primary citation

Tallant, C.,Garcia-Castellanos, R.,Seco, J.,Baumann, U.,Gomis-Ruth, F.X.
Molecular Analysis of Ulilysin, the Structural Prototype of a New Family of Metzincin Metalloproteases.
J.Biol.Chem., 281:17920-, 2006

PubMed Abstract: The metzincin clan encompasses several families of zinc-dependent metalloproteases with proven function both in physiology and pathology. They act either as broad spectrum protein degraders or as sheddases, operating through limited proteolysis. Among the structurally uncharacterized metzincin families are the pappalysins, of which the most thoroughly studied member is human pregnancy-associated plasma protein A (PAPP-A), a heavily glycosylated 170-kDa multidomain protein specifically cleaving insulin-like growth factor (IGF)-binding proteins (IGFBPs). Proulilysin is a 38-kDa archaeal protein that shares sequence similarity with PAPP-A but encompasses only the pro-domain and the catalytic domain. It undergoes calcium-mediated autolytic activation, and the mature protein adopts a three-dimensional structure with two subdomains separated by an active site cleft containing the catalytic zinc ion. This structure is reminiscent of human members of the adamalysin/ADAMs (a disintegrin and a metalloprotease) family of metzincins. A bound dipeptide yields information on the substrate specificity of ulilysin, which specifically hydrolyzes IGFBP-2 to -6, insulin, and extracellular matrix proteins but not IGFBP-1 or IGF-II. Accordingly, ulilysin has higher proteolytic efficiency and a broader substrate specificity than human PAPP-A. The structure of ulilysin represents a prototype for the catalytic domain of pappalysins.

PubMed: 16627477
DOI: 10.1074/JBC.M600907200

Experimental method

X-RAY DIFFRACTION (1.7 Å)