1PL4

Crystal Structure of human MnSOD Y166F mutant


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.47 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Amino acid substitution at the dimeric interface of human manganese superoxide dismutase

Hearn, A.S.Fan, L.Lepock, J.R.Luba, J.P.Greenleaf, W.B.Cabelli, D.E.Tainer, J.A.Nick, H.S.Silverman, D.N.

(2004) J Biol Chem 279: 5861-5866

  • DOI: https://doi.org/10.1074/jbc.M311310200
  • Primary Citation of Related Structures:  
    1PL4, 1PM9

  • PubMed Abstract: 

    The side chains of His30 and Tyr166 from adjacent subunits in the homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the dimer interface and participate in a hydrogen-bonded network that extends to the active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant showed 10-fold decreases in steady-state constants for catalysis measured by pulse radiolysis. The observation of no additional effect upon the second mutation is an example of cooperatively interacting residues. A similar effect was observed in the thermal stability of these enzymes; the double mutant did not reduce the major unfolding transition to an extent greater than either single mutant. The crystal structures of these site-specific mutants each have unique conformational changes, but each has lost the hydrogen bond across the dimer interface, which results in a decrease in catalysis. These same mutations caused an enhancement of the dissociation of the product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex. This would have a selective advantage in blocking a cellular overproduction of toxic H2O2.


  • Organizational Affiliation

    Departments of Pharmacology and Neuroscience, University of Florida, Gainesville, Florida 32610-0267, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Superoxide dismutase [Mn], mitochondrial
A, B, C, D
198Homo sapiensMutation(s): 1 
EC: 1.15.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P04179 (Homo sapiens)
Explore P04179 
Go to UniProtKB:  P04179
PHAROS:  P04179
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04179
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.47 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.200 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.689α = 90
b = 77.711β = 90
c = 135.795γ = 90
Software Package:
Software NamePurpose
SHELXLrefinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-16
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.5: 2023-08-16
    Changes: Data collection, Refinement description