3A8I

Crystal Structure of ET-EHred-5-CH3-THF complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.185 

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This is version 1.3 of the entry. See complete history


Literature

Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system: implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism

Okamura-Ikeda, K.Hosaka, H.Maita, N.Fujiwara, K.Yoshizawa, A.C.Nakagawa, A.Taniguchi, H.

(2010) J Biol Chem 285: 18684-18692

  • DOI: https://doi.org/10.1074/jbc.M110.110718
  • Primary Citation of Related Structures:  
    3A8I, 3A8J, 3A8K, 3AB9

  • PubMed Abstract: 

    Aminomethyltransferase, a component of the glycine cleavage system termed T-protein, reversibly catalyzes the degradation of the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein, resulting in the production of ammonia, 5,10-methylenetetrahydrofolate, and dihydrolipoate-bearing H-protein in the presence of tetrahydrofolate. Several mutations in the human T-protein gene are known to cause nonketotic hyperglycinemia. Here, we report the crystal structure of Escherichia coli T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate, a complex mimicking the ternary complex in the reverse reaction. The structure of the complex shows a highly interacting intermolecular interface limited to a small area and the protein-bound dihydrolipoyllysine arm inserted into the active site cavity of the T-protein. Invariant Arg(292) of the T-protein is essential for complex assembly. The structure also provides novel insights in understanding the disease-causing mutations, in addition to the disease-related impairment in the cofactor-enzyme interactions reported previously. Furthermore, structural and mutational analyses suggest that the reversible transfer of the methylene group between the lipoate and tetrahydrofolate should proceed through the electron relay-assisted iminium intermediate formation.


  • Organizational Affiliation

    Institute for Enzyme Research, the University of Tokushima, Tokushima 770-8503, Japan. ikeda@ier.tokushima-u.ac.jp


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aminomethyltransferase
A, B, C, D
364Escherichia coli K-12Mutation(s): 0 
EC: 2.1.2.10
UniProt
Find proteins for P27248 (Escherichia coli (strain K12))
Explore P27248 
Go to UniProtKB:  P27248
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27248
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Glycine cleavage system H protein
E, F
129Escherichia coli K-12Mutation(s): 0 
UniProt
Find proteins for P0A6T9 (Escherichia coli (strain K12))
Explore P0A6T9 
Go to UniProtKB:  P0A6T9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0A6T9
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.185 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.985α = 91.53
b = 88.928β = 102.47
c = 97.993γ = 89.59
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2013-08-21
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description