| http://purl.uniprot.org/citations/17157876 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17157876 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17157876 | http://www.w3.org/2000/01/rdf-schema#comment | "Human carboxypeptidase N (CPN), a member of the CPN/E subfamily of "regulatory" metallo-carboxypeptidases, is an extracellular glycoprotein synthesized in the liver and secreted into the blood, where it controls the activity of vasoactive peptide hormones, growth factors and cytokines by specifically removing C-terminal basic residues. Normally, CPN circulates in blood plasma as a hetero-tetramer consisting of two 83 kDa (CPN2) domains each flanked by a 48 to 55 kDa catalytic (CPN1) domain. We have prepared and crystallized the recombinant C-terminally truncated catalytic domain of human CPN1, and have determined and refined its 2.1 A crystal structure. The structural analysis reveals that CPN1 has a pear-like shape, consisting of a 319 residue N-terminal catalytic domain and an abutting, cylindrically shaped 79 residue C-terminal beta-sandwich transthyretin (TT) domain, more resembling CPD-2 than CPM. Like these other CPN/E members, two surface loops surrounding the active-site groove restrict access to the catalytic center, offering an explanation for why some larger protein carboxypeptidase inhibitors do not inhibit CPN. Modeling of the Pro-Phe-Arg C-terminal end of the natural substrate bradykinin into the active site shows that the S1' pocket of CPN1 might better accommodate P1'-Lys than Arg residues, in agreement with CPN's preference for cleaving off C-terminal Lys residues. Three Thr residues at the distal TT edge of CPN1 are O-linked to N-acetyl glucosamine sugars; equivalent sites in the membrane-anchored CPM are occupied by basic residues probably involved in membrane interaction. In tetrameric CPN, each CPN1 subunit might interact with the central leucine-rich repeat tandem of the cognate CPN2 subunit via a unique hydrophobic surface patch wrapping around the catalytic domain-TT interface, exposing the two active centers."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2006.11.025"xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2006.11.025"xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Huber R."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Huber R."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Bode W."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Bode W."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Hoopes J.T."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Hoopes J.T."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Tan F."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Tan F."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Erdos E.G."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Erdos E.G."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Skidgel R.A."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Skidgel R.A."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Maskos K."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Maskos K."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Deddish P.A."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Deddish P.A."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Keil C."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Keil C."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Than M."xsd:string |
| http://purl.uniprot.org/citations/17157876 | http://purl.uniprot.org/core/author | "Than M."xsd:string |