Nucleic Acids Research, 2000, Vol. 28, No. 11 2229-2233
© 2000 Oxford University Press
Two tricks in one bundle: helix–turn–helix gains enzymatic activity
Biochemistry Department, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA
Many examples of enzymes that have lost their catalytic activity and perform other biological functions are known. The opposite situation is rare. A previously unnoticed structural similarity between the 
integrase family (Int) proteins and the AraC family of transcriptional activators implies that the Int family evolved by duplication of an ancient DNA-binding homeodomain-like module, which acquired enzymatic activity. The two helix–turn–helix (HTH) motifs in Int proteins incorporate catalytic residues and participate in DNA binding. The active site of Int proteins, which include the type IB topoisomerases, is formed at the domain interface and the catalytic tyrosine residue is located in the second helix of the C-terminal HTH motif. Structural analysis of other ‘tyrosine’ DNA-breaking/rejoining enzymes with similar enzyme mechanisms, namely prokaryotic topoisomerase I, topoisomerase II and archaeal topoisomerase VI, reveals that the catalytic tyrosine is placed in a HTH domain as well. Surprisingly, the location of this tyrosine residue in the structure is not conserved, suggesting independent, parallel evolution leading to the same catalytic function by homologous HTH domains. The ‘tyrosine’ recombinases give a rare example of enzymes that evolved from ancient DNA-binding modules and present a unique case for homologous enzymatic domains with similar catalytic mechanisms but different locations of catalytic residues, which are placed at non-homologous sites.
* Tel: +1 214 648 3386; Fax: +1 214 648 9099; Email: grishin@chop.swmed.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Balaji and L. Aravind The RAGNYA fold: a novel fold with multiple topological variants found in functionally diverse nucleic acid, nucleotide and peptide-binding proteins Nucleic Acids Res., September 27, 2007; 35(17): 5658 - 5671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Martinez, J. A. Bengoechea, and F. Cuttitta Molecular Evolution of Proadrenomedullin N-Terminal 20 Peptide (PAMP): Evidence for Gene Co-Option Endocrinology, July 1, 2006; 147(7): 3457 - 3461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen and P. A. Rice The Role of the Conserved Trp330 in Flp-mediated Recombination: FUNCTIONAL AND STRUCTURAL ANALYSIS J. Biol. Chem., June 27, 2003; 278(27): 24800 - 24807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Bankhead, B. J. Etzel, F. Wolven, S. Bordenave, J. L. Boldt, T. A. Larsen, and A. M. Segall Mutations at Residues 282, 286, and 293 of Phage {lambda} Integrase Exert Pathway-Specific Effects on Synapsis and Catalysis in Recombination J. Bacteriol., April 15, 2003; 185(8): 2653 - 2666. [Abstract] [Full Text] [PDF]
|
|