1TR4

Solution structure of human oncogenic protein gankyrin


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 80 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations,structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Solution structure of the human oncogenic protein gankyrin containing seven ankyrin repeats and analysis of its structure--function relationship.

Yuan, C.Li, J.Mahajan, A.Poi, M.J.Byeon, I.J.Tsai, M.D.

(2004) Biochemistry 43: 12152-12161

  • DOI: https://doi.org/10.1021/bi049116o
  • Primary Citation of Related Structures:  
    1TR4

  • PubMed Abstract: 

    Human gankyrin (226 residues, 24.4 kDa) is a liver oncoprotein that plays an important role in the development of human hepatocellular carcinomas. In this paper, its solution structure is reported, which is the largest ankyrin protein ever determined by NMR. The highly degenerate primary sequences of the seven ankyrin repeats presented a major challenge, which was overcome by combined use of TROSY experiments, perdeuterated samples, isotope-filtered NMR experiments, and residual dipolar couplings. The final structure was of high quality, with atomic rmsds for the backbone (N, C', and C(alpha)) and all heavy atoms (residues 4-224) of 0.69 +/- 0.09 and 1.04 +/- 0.09 A, respectively. Detailed analyses of NMR data suggested that the conserved TPLH motifs play important structural roles in stabilizing the repeating ankyrin scaffold. Gankyrin is conformationally more stable than the tumor suppressor p16(INK4A), possibly due to the structural roles of conserved residues evidenced by slowly exchanging backbone amides as well as hydrogen bonding networks involving labile side chain protons. Structural comparison with p16(INK4A) identified several residues of gankyrin that are potentially important for CDK4 binding, whereas observation of the thiol proton of C180 indicated a well-structured Rb-binding site in the helical region of the sixth ankyrin repeat. Interestingly, the CDK4-binding site and Rb-binding site located in N- and C-terminal regions, respectively, are separated by comparatively more stable ankyrin repeats and highly condensed positive surface charge. These results and analyses will shed light on the structural basis of the function of human gankyrin.


  • Organizational Affiliation

    Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA. cyuan@ccic.ohio-state.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 10226Homo sapiensMutation(s): 0 
Gene Names: PSMD10
UniProt & NIH Common Fund Data Resources
Find proteins for O75832 (Homo sapiens)
Explore O75832 
Go to UniProtKB:  O75832
PHAROS:  O75832
GTEx:  ENSG00000101843 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75832
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 80 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations,structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-11-16
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-03-02
    Changes: Data collection, Database references, Derived calculations