2nsm

Crystal structure of the human carboxypeptidase N (Kininase I) catalytic domainCrystal structure of the human carboxypeptidase N (Kininase I) catalytic domain

Structural highlights 2nsm is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Activity: Lysine carboxypeptidase, with EC number 3.4.17.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [CBPN_HUMAN] Defects in CPN1 are the cause of carboxypeptidase N deficiency (CPND) [MIM:212070]. Patients affected present some combination of angioedema or chronic urticaria, as well as hay fever or astma, and have also slightly depressed serum carboxy peptidase N, suggestive of autosomal recessive inheritance of this disorder. Function [CBPN_HUMAN] Protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Crystal structure of the human carboxypeptidase N (kininase I) catalytic domain.,Keil C, Maskos K, Than M, Hoopes JT, Huber R, Tan F, Deddish PA, Erdos EG, Skidgel RA, Bode W J Mol Biol. 2007 Feb 16;366(2):504-16. Epub 2006 Nov 11. PMID:17157876 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carboxypeptidase

spinqualitylabelsall models 2nsm, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image