4ENO

Crystal structure of oxidized human nm23-H1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structure of Nm23-H1 under oxidative conditions.

Kim, M.S.Jeong, J.Jeong, J.Shin, D.H.Lee, K.J.

(2013) Acta Crystallogr D Biol Crystallogr 69: 669-680

  • DOI: https://doi.org/10.1107/S0907444913001194
  • Primary Citation of Related Structures:  
    4ENO

  • PubMed Abstract: 

    Nm23-H1/NDPK-A, a tumour metastasis suppressor, is a multifunctional housekeeping enzyme with nucleoside diphosphate kinase activity. Hexameric Nm23-H1 is required for suppression of tumour metastasis and it is dissociated into dimers under oxidative conditions. Here, the crystal structure of oxidized Nm23-H1 is presented. It reveals the formation of an intramolecular disulfide bond between Cys4 and Cys145 that triggers a large conformational change that destabilizes the hexameric state. The dependence of the dissociation dynamics on the H2O2 concentration was determined using hydrogen/deuterium-exchange experiments. The quaternary conformational change provides a suitable environment for the oxidation of Cys109 to sulfonic acid, as demonstrated by peptide sequencing using nanoUPLC-ESI-q-TOF tandem MS. From these and other data, it is proposed that the molecular and cellular functions of Nm23-H1 are regulated by a series of oxidative modifications coupled to its oligomeric states and that the modified cysteines are resolvable by NADPH-dependent reduction systems. These findings broaden the understanding of the complicated enzyme-regulatory mechanisms that operate under oxidative conditions.


  • Organizational Affiliation

    The Center for Cell Signaling and Drug Discovery Research, College of Pharmacy, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nucleoside diphosphate kinase A
A, B
152Homo sapiensMutation(s): 0 
Gene Names: NME1NDPKANM23
EC: 2.7.4.6
UniProt & NIH Common Fund Data Resources
Find proteins for P15531 (Homo sapiens)
Explore P15531 
Go to UniProtKB:  P15531
PHAROS:  P15531
GTEx:  ENSG00000239672 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15531
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.190 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106.768α = 90
b = 106.768β = 90
c = 106.768γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
EPMRphasing
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHENIXrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-27
    Type: Initial release
  • Version 1.1: 2019-12-25
    Changes: Database references