Three-dimensional models and structure analysis of corynemycolyltransferases in Corynebacterium glutamicum and Corynebacterium efficiens

Int J Biol Macromol. 2004 Jun;34(3):181-9. doi: 10.1016/j.ijbiomac.2004.03.008.

Abstract

The corynemycolyltransferase proteins were identified from Corynebacterium glutamicum and Corynebacterium efficiens genomes using computational tools available in the public domain. Three-dimensional models were constructed for corynemycolyltransferases based on the crystal structures of related mycolyltransferases in Mycobacterium tuberculosis using the comparative modeling methods. The corynemycolyltransferases share overall an alpha/beta-fold characteristic of the mycolyltransferases despite low sequence identity (<20%) shared by some of the corynemycolyltransferases. However, a significant difference is observed in the region between amino acid residues Trp82-Trp97 and Ala222-Asn223 corresponding to mycolyltransferases. The specificity pockets defined by interactions with the trehalose substrate observed in the crystal structure complex of Ag85B mycolyltransferase (PDB code: 1F0P) suggests that trehalose may not bind some corynemycolyltransferases. This is due to critical mutations in corynemycolyltransferase binding subsites that lead to loss of equivalent side-chain interactions with trehalose and unfavorable steric interactions, particularly, in the case of cmytC gene and the protein corresponding to the gene identifier CE0356 with the equivalent Ala222-Asn223 "long insertion loop". Further, the fibronectin binding region (Phe58-Val69), in mycolyltransferases associated with mediating host-pathogen interactions in M. tuberculosis comprises amino acid residue mutations in the corresponding region in the soil bacterium--Corynebacterium corynemycolyltransferases, that suggest a different epitope and therefore possible lack of binding to fibronectin. The corynemycolyltransferase cmytA responsible for the cell shape formation and for maintaining the cell surface integrity is associated with a C-terminal domain that we have recently shown to comprise tandem amino acid sequence repeats that is likely to be associated with a regular secondary structural motif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / chemistry*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Corynebacterium / enzymology*
  • Corynebacterium / genetics
  • Genome
  • Models, Chemical*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Structural Homology, Protein*
  • Trehalose / chemistry

Substances

  • Bacterial Proteins
  • Trehalose
  • Acyltransferases