7BSL

Crystal Structure of human ME2 R67A mutant


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.252 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P) + -dependent malic enzyme.

Hsieh, J.Y.Yang, H.P.Tewary, S.K.Cheng, H.C.Liu, Y.L.Tai, S.C.Chen, W.L.Hsu, C.H.Huang, T.J.Chou, C.J.Huang, Y.N.Peng, C.T.Ho, M.C.Liu, G.Y.Hung, H.C.

(2021) iScience 24: 102034-102034

  • DOI: https://doi.org/10.1016/j.isci.2021.102034
  • Primary Citation of Related Structures:  
    7BSJ, 7BSK, 7BSL

  • PubMed Abstract: 

    Human mitochondrial NAD(P) + -dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. Two ME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating "dead form," and ME2_R484W was an overactivating "closed form" of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes.


  • Organizational Affiliation

    Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NAD-dependent malic enzyme, mitochondrial
A, B
566Homo sapiensMutation(s): 1 
Gene Names: ME2
EC: 1.1.1.38
UniProt & NIH Common Fund Data Resources
Find proteins for P23368 (Homo sapiens)
Explore P23368 
Go to UniProtKB:  P23368
PHAROS:  P23368
GTEx:  ENSG00000082212 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23368
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.252 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.199α = 90
b = 191.146β = 90
c = 59.091γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
PDB_EXTRACTdata extraction
PHENIXphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Ministry of Science and Technology (MoST, Taiwan)Taiwan--
Academia Sinica (Taiwan)Taiwan--

Revision History  (Full details and data files)

  • Version 1.0: 2021-02-10
    Type: Initial release
  • Version 1.1: 2021-02-24
    Changes: Database references
  • Version 1.2: 2023-11-29
    Changes: Data collection, Database references, Refinement description