3MFW

Crystal structure of human arginase I in complex with L-2-aminohistidine and sulphate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.47 Å
  • R-Value Free: 0.162 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.149 

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This is version 1.2 of the entry. See complete history


Literature

2-aminoimidazole amino acids as inhibitors of the binuclear manganese metalloenzyme human arginase I.

Ilies, M.Di Costanzo, L.North, M.L.Scott, J.A.Christianson, D.W.

(2010) J Med Chem 53: 4266-4276

  • DOI: https://doi.org/10.1021/jm100306a
  • Primary Citation of Related Structures:  
    3MFV, 3MFW

  • PubMed Abstract: 

    Arginase, a key metalloenzyme of the urea cycle that converts L-arginine into L-ornithine and urea, is presently considered a pharmaceutical target for the management of diseases associated with aberrant l-arginine homeostasis, such as asthma, cardiovascular diseases, and erectile dysfunction. We now report the design, synthesis, and evaluation of a series of 2-aminoimidazole amino acid inhibitors in which the 2-aminoimidazole moiety serves as a guanidine mimetic. These compounds represent a new class of arginase inhibitors. The most potent inhibitor identified in this study, 2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid (A1P, 10), binds to human arginase I with K(d) = 2 microM and significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation. These findings suggest that 2-aminoimidazole amino acids represent new leads for the development of arginase inhibitors with promising pharmacological profiles.


  • Organizational Affiliation

    Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Arginase-1
A, B
322Homo sapiensMutation(s): 0 
Gene Names: ARG1
EC: 3.5.3.1
UniProt & NIH Common Fund Data Resources
Find proteins for P05089 (Homo sapiens)
Explore P05089 
Go to UniProtKB:  P05089
PHAROS:  P05089
GTEx:  ENSG00000118520 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05089
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
B3U PDBBind:  3MFW Ki: 3.00e+5 (nM) from 1 assay(s)
BindingDB:  3MFW Ki: 3.00e+5 (nM) from 1 assay(s)
Binding MOAD:  3MFW Ki: 3.00e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.47 Å
  • R-Value Free: 0.162 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.149 
  • Space Group: P 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 90.338α = 90
b = 90.338β = 90
c = 69.429γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
CNSrefinement
HKL-2000data reduction
SCALEPACKdata 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: 2010-05-05
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description