2GCE

The 1,1-proton transfer reaction mechanism by alpha-methylacyl-CoA racemase is catalyzed by an aspartate/histidine pair and involves a smooth, methionine-rich surface for binding the fatty acyl moiety


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.202 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

The Catalysis of the 1,1-Proton Transfer by alpha-Methyl-acyl-CoA Racemase Is Coupled to a Movement of the Fatty Acyl Moiety Over a Hydrophobic, Methionine-rich Surface

Bhaumik, P.Schmitz, W.Hassinen, A.Hiltunen, J.K.Conzelmann, E.Wierenga, R.K.

(2007) J Mol Biol 367: 1145-1161

  • DOI: https://doi.org/10.1016/j.jmb.2007.01.062
  • Primary Citation of Related Structures:  
    2GCE, 2GCI, 2GD0, 2GD2, 2GD6

  • PubMed Abstract: 

    Alpha-methylacyl-CoA racemases are essential enzymes for branched-chain fatty acid metabolism. Their reaction mechanism and the structural basis of their wide substrate specificity are poorly understood. High-resolution crystal structures of Mycobacterium tuberculosis alpha-methylacyl-CoA racemase (MCR) complexed with substrate molecules show the active site geometry required for catalysis of the interconversion of (2S) and (2R)-methylacyl-CoA. The thioester oxygen atom and the 2-methyl group are in a cis-conformation with respect to each other. The thioester oxygen atom fits into an oxyanion hole and the 2-methyl group points into a hydrophobic pocket. The active site geometry agrees with a 1,1-proton transfer mechanism in which the acid/base-pair residues are His126 and Asp156. The structures of the complexes indicate that the acyl chains of the S-substrate and the R-substrate bind in an S-pocket and an R-pocket, respectively. A unique feature of MCR is a large number of methionine residues in the acyl binding region, located between the S-pocket and the R-pocket. It appears that the (S) to (R) interconversion of the 2-methylacyl chiral center is coupled to a movement of the acyl group over this hydrophobic, methionine-rich surface, when moving from its S-pocket to its R-pocket, whereas the 2-methyl moiety and the CoA group remain fixed in their respective pockets.


  • Organizational Affiliation

    Biocenter Oulu and Department of Biochemistry, University of Oulu, Linnanmaa, P.O. Box 3000, FIN-90014 University of Oulu, Finland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
probable alpha-methylacyl-CoA racemase MCR
A, B, C, D
360Mycobacterium tuberculosisMutation(s): 0 
Gene Names: CAB09031
EC: 5.1.99.4
UniProt
Find proteins for O06543 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore O06543 
Go to UniProtKB:  O06543
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO06543
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
SFC Binding MOAD:  2GCE Kd: 2.45e+4 (nM) from 1 assay(s)
RFC Binding MOAD:  2GCE Kd: 2.45e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.202 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 179.95α = 90
b = 79.58β = 90.07
c = 117.43γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MAR345data collection
XDSdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-02-20
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary