4GWD

Crystal Structure of the Mn2+2,Zn2+-Human Arginase I-ABH Complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.53 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.160 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structure and function of non-native metal clusters in human arginase I.

D'Antonio, E.L.Hai, Y.Christianson, D.W.

(2012) Biochemistry 51: 8399-8409

  • DOI: https://doi.org/10.1021/bi301145n
  • Primary Citation of Related Structures:  
    4GSM, 4GSV, 4GSZ, 4GWC, 4GWD

  • PubMed Abstract: 

    Various binuclear metal ion clusters and complexes have been reconstituted in crystalline human arginase I by removing the Mn(2+)(2) cluster of the wild-type enzyme with metal chelators and subsequently soaking the crystalline apoenzyme in buffer solutions containing NiCl(2) or ZnCl(2). X-ray crystal structures of these metal ion variants are correlated with catalytic activity measurements that reveal differences resulting from metal ion substitution. Additionally, treatment of crystalline Mn(2+)(2)-human arginase I with Zn(2+) reveals for the first time the structural basis for inhibition by Zn(2+), which forms a carboxylate-histidine-Zn(2+) triad with H141 and E277. The imidazole side chain of H141 is known to be hyper-reactive, and its chemical modification or mutagenesis is known to similarly compromise catalysis. The reactive substrate analogue 2(S)-amino-6-boronohexanoic acid (ABH) binds as a tetrahedral boronate anion to Mn(2+)(2), Co(2+)(2), Ni(2+)(2), and Zn(2+)(2) clusters in human arginase I, and it can be stabilized by a third inhibitory Zn(2+) ion coordinated by H141. Because ABH binds as an analogue of the tetrahedral intermediate and its flanking transition states in catalysis, this implies that the various metallo-substituted enzymes are capable of some level of catalysis with an actual substrate. Accordingly, we establish the following trend for turnover number (k(cat)) and catalytic efficiency (k(cat)/K(M)): Mn(2+) > Ni(2+) ≈ Co(2+) ≫ Zn(2+). Therefore, Mn(2+) is required for optimal catalysis by human arginase I.


  • Organizational Affiliation

    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 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
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ABH
Query on ABH

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B]
2(S)-AMINO-6-BORONOHEXANOIC ACID
C6 H15 B N O5
BLVGFZFOWWBCCZ-YFKPBYRVSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
MN
Query on MN

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
G [auth B],
H [auth B]
MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.53 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.160 
  • Space Group: P 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.082α = 90
b = 91.082β = 90
c = 69.903γ = 120
Software Package:
Software NamePurpose
CBASSdata collection
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-26
    Type: Initial release
  • Version 1.1: 2012-11-14
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description