2CI4

Crystal Structure of Dimethylarginine dimethylaminohydrolase I crystal form II


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.199 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure of the Mammalian Nos Regulator Dimethylarginine Dimethylaminohydrolase: A Basis for the Design of Specific Inhibitors.

Frey, D.Braun, O.Briand, C.Vasak, M.Grutter, M.G.

(2006) Structure 14: 901

  • DOI: https://doi.org/10.1016/j.str.2006.03.006
  • Primary Citation of Related Structures:  
    2C6Z, 2CI1, 2CI3, 2CI4, 2CI5, 2CI6, 2CI7

  • PubMed Abstract: 

    Dimethylarginine dimethylaminohydrolase (DDAH) is involved in the regulation of nitric oxide synthase (NOS) by metabolizing the free endogenous arginine derivatives N(omega)-methyl-L-arginine (MMA) and N(omega),N(omega)-dimethyl-L-arginine (ADMA), which are competitive inhibitors of NOS. Here, we present high-resolution crystal structures of DDAH isoform 1 (DDAH-1) isolated from bovine brain in complex with different inhibitors, including S-nitroso-L-homocysteine and Zn2+, a regulator of this mammalian enzyme. The structure of DDAH-1 consists of a propeller-like fold similar to other arginine-modifying enzymes and a flexible loop, which adopts different conformations and acts as a lid at the entrance of the active site. The orientation and interaction mode of inhibitors in the active site give insight into the regulation and the molecular mechanism of the enzyme. The presented structures provide a basis for the structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases.


  • Organizational Affiliation

    Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NG, NG-DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 1284Bos taurusMutation(s): 0 
EC: 3.5.3.18
UniProt
Find proteins for P56965 (Bos taurus)
Explore P56965 
Go to UniProtKB:  P56965
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56965
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.199 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.84α = 90
b = 81.015β = 100.59
c = 44.675γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-05-17
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description