3FJU

Ascaris suum carboxypeptidase inhibitor in complex with human carboxypeptidase A1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite

Sanglas, L.Aviles, F.X.Huber, R.Gomis-Ruth, F.X.Arolas, J.L.

(2009) Proc Natl Acad Sci U S A 106: 1743-1747

  • DOI: https://doi.org/10.1073/pnas.0812623106
  • Primary Citation of Related Structures:  
    3FJU

  • PubMed Abstract: 

    Roundworms of the genus Ascaris are common parasites of the human gastrointestinal tract. A battery of selective inhibitors protects them from host enzymes and the immune system. Here, a metallocarboxypeptidase (MCP) inhibitor, ACI, was identified in protein extracts from Ascaris by intensity-fading MALDI-TOF mass spectrometry. The 67-residue amino acid sequence of ACI showed no significant homology with any known protein. Heterologous overexpression and purification of ACI rendered a functional molecule with nanomolar equilibrium dissociation constants against MCPs, which denoted a preference for digestive and mast cell A/B-type MCPs. Western blotting and immunohistochemistry located ACI in the body wall, intestine, female reproductive tract, and fertilized eggs of Ascaris, in accordance with its target specificity. The crystal structure of the complex of ACI with human carboxypeptidase A1, one of its potential targets in vivo, revealed a protein with a fold consisting of two tandem homologous domains, each containing a beta-ribbon and two disulfide bonds. These domains are connected by an alpha-helical segment and a fifth disulfide bond. Binding and inhibition are exerted by the C-terminal tail, which enters the funnel-like active-site cavity of the enzyme and approaches the catalytic zinc ion. The findings reported provide a basis for the biological function of ACI, which may be essential for parasitic survival during infection.


  • Organizational Affiliation

    Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Facultat de Ciències, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Barcelona, Spain.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carboxypeptidase A1307Homo sapiensMutation(s): 0 
Gene Names: CPA1CPA
EC: 3.4.17.1
UniProt & NIH Common Fund Data Resources
Find proteins for P15085 (Homo sapiens)
Explore P15085 
Go to UniProtKB:  P15085
PHAROS:  P15085
GTEx:  ENSG00000091704 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15085
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Carboxypeptidase A inhibitor65Ascaris suumMutation(s): 0 
UniProt
Find proteins for P19399 (Ascaris suum)
Explore P19399 
Go to UniProtKB:  P19399
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19399
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CAC
Query on CAC

Download Ideal Coordinates CCD File 
M [auth A],
N [auth A],
O [auth A],
P [auth A]
CACODYLATE ION
C2 H6 As O2
OGGXGZAMXPVRFZ-UHFFFAOYSA-M
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
W [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
Q [auth A]
R [auth A]
S [auth A]
T [auth A]
U [auth A]
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
U [auth A],
V [auth A]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
L [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.47α = 90
b = 78.7β = 90
c = 84.5γ = 90
Software Package:
Software NamePurpose
ProDCdata collection
AMoREphasing
REFMACrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-12-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description