2NSM

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 

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This is version 1.4 of the entry. See complete history


Literature

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

Keil, C.Maskos, K.Than, M.Hoopes, J.T.Huber, R.Tan, F.Deddish, P.A.Erdoes, E.G.Skidgel, R.A.Bode, W.

(2007) J Mol Biol 366: 504-516

  • DOI: https://doi.org/10.1016/j.jmb.2006.11.025
  • Primary Citation of Related Structures:  
    2NSM

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Arbeitsgruppe Proteinaseforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18, D-82152 Planegg-Martinsried, Germany.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carboxypeptidase N catalytic chain439Homo sapiensMutation(s): 0 
EC: 3.4.17.3
UniProt & NIH Common Fund Data Resources
Find proteins for P15169 (Homo sapiens)
Explore P15169 
Go to UniProtKB:  P15169
PHAROS:  P15169
GTEx:  ENSG00000120054 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15169
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 150.03α = 90
b = 150.03β = 90
c = 54.91γ = 120
Software Package:
Software NamePurpose
DNAdata collection
PHASERphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-04-24
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Database references, Derived calculations, Structure summary
  • Version 1.4: 2023-10-25
    Changes: Advisory, Data collection, Database references, Refinement description, Structure summary