5HIL

Crystal structure of glycine sarcosine N-methyltransferase from Methanohalophilus portucalensis in complex with S-adenosylhomocysteine and sarcosine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.47 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.169 

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This is version 1.2 of the entry. See complete history


Literature

Structural Analysis of Glycine Sarcosine N-methyltransferase from Methanohalophilus portucalensis Reveals Mechanistic Insights into the Regulation of Methyltransferase Activity

Lee, Y.R.Lin, T.S.Lai, S.J.Liu, M.S.Lai, M.C.Chan, N.L.

(2016) Sci Rep 6: 38071-38071

  • DOI: https://doi.org/10.1038/srep38071
  • Primary Citation of Related Structures:  
    5GWX, 5H02, 5HII, 5HIJ, 5HIK, 5HIL, 5HIM

  • PubMed Abstract: 

    Methyltransferases play crucial roles in many cellular processes, and various regulatory mechanisms have evolved to control their activities. For methyltransferases involved in biosynthetic pathways, regulation via feedback inhibition is a commonly employed strategy to prevent excessive accumulation of the pathways' end products. To date, no biosynthetic methyltransferases have been characterized by X-ray crystallography in complex with their corresponding end product. Here, we report the crystal structures of the glycine sarcosine N-methyltransferase from the halophilic archaeon Methanohalophilus portucalensis (MpGSMT), which represents the first structural elucidation of the GSMT methyltransferase family. As the first enzyme in the biosynthetic pathway of the osmoprotectant betaine, MpGSMT catalyzes N-methylation of glycine and sarcosine, and its activity is feedback-inhibited by the end product betaine. A structural analysis revealed that, despite the simultaneous presence of both substrate (sarcosine) and cofactor (S-adenosyl-L-homocysteine; SAH), the enzyme was likely crystallized in an inactive conformation, as additional structural changes are required to complete the active site assembly. Consistent with this interpretation, the bound SAH can be replaced by the methyl donor S-adenosyl-L-methionine without triggering the methylation reaction. Furthermore, the observed conformational state was found to harbor a betaine-binding site, suggesting that betaine may inhibit MpGSMT activity by trapping the enzyme in an inactive form. This work implicates a structural basis by which feedback inhibition of biosynthetic methyltransferases may be achieved.


  • Organizational Affiliation

    Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glycine sarcosine N-methyltransferase284Methanohalophilus portucalensis FDF-1Mutation(s): 0 
Gene Names: gsmt
EC: 2.1.1.156
UniProt
Find proteins for F6KV61 (Methanohalophilus portucalensis FDF-1)
Explore F6KV61 
Go to UniProtKB:  F6KV61
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupF6KV61
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.47 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.169 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.897α = 90
b = 121.124β = 90
c = 131.589γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Blu-Icedata collection
HKL-2000data scaling
HKL-2000data processing
PHENIXmodel building

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Ministry of Science and TechnologyTaiwanNSC101-2911-I-002-303, 103-2113-M-002-010-MY3, 104-2911-I-002-302
National Taiwan UniversityTaiwan104R7614-3 and 104R7560-4
Ministry of Education, Taiwan ROC, under the ATU plan to NLCTaiwanNational Chung Hsing University

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-23
    Type: Initial release
  • Version 1.1: 2017-01-18
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description