2UYQ

Crystal structure of ML2640c from Mycobacterium leprae in complex with S-adenosylmethionine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

The Crystal Structure of M. Leprae Ml2640C Defines a Large Family of Putative S-Adenosylmethionine- Dependent Methyltransferases in Mycobacteria.

Grana, M.Haouz, A.Buschiazzo, A.Miras, I.Wehenkel, A.Bondet, V.Shepard, W.Schaeffer, F.Cole, S.T.Alzari, P.M.

(2007) Protein Sci 16: 1896

  • DOI: https://doi.org/10.1110/ps.072982707
  • Primary Citation of Related Structures:  
    2CKD, 2UYO, 2UYQ

  • PubMed Abstract: 

    Mycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTase). As part of a Structural Genomics initiative on conserved hypothetical proteins in pathogenic mycobacteria, we have determined the structure of ML2640c in two distinct crystal forms. As expected, ML2640c has a typical MTase core domain and binds the methyl donor substrate AdoMet in a manner consistent with other known members of this structural family. The putative acceptor substrate-binding site of ML2640c is a large internal cavity, mostly lined by aromatic and aliphatic side-chain residues, suggesting that a lipid-like molecule might be targeted for catalysis. A flap segment (residues 222-256), which isolates the binding site from the bulk solvent and is highly mobile in the crystal structures, could serve as a gateway to allow substrate entry and product release. The multiple sequence alignment of ML2640c-like proteins revealed that the central alpha/beta core and the AdoMet-binding site are very well conserved within the family. However, the amino acid positions defining the binding site for the acceptor substrate display a higher variability, suggestive of distinct acceptor substrate specificities. The ML2640c crystal structures offer the first structural glimpses at this important family of mycobacterial proteins and lend strong support to their functional assignment as AdoMet-dependent methyltransferases.


  • Organizational Affiliation

    Unité de Biochimie Structurale (CNRS-URA 2185), Institut Pasteur, 75724 Paris, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HYPOTHETICAL PROTEIN ML2640310Mycobacterium lepraeMutation(s): 0 
UniProt
Find proteins for Q9CCZ4 (Mycobacterium leprae (strain TN))
Explore Q9CCZ4 
Go to UniProtKB:  Q9CCZ4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9CCZ4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAM
Query on SAM

Download Ideal Coordinates CCD File 
B [auth A]S-ADENOSYLMETHIONINE
C15 H22 N6 O5 S
MEFKEPWMEQBLKI-FCKMPRQPSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SAM Binding MOAD:  2UYQ Kd: 2100 (nM) from 1 assay(s)
PDBBind:  2UYQ Kd: 2100 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.826α = 90
b = 75.826β = 90
c = 105.655γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-08-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description