PMID: 12767827May 28, 2003Paper

Dynamics and DNA substrate recognition by the catalytic domain of lambda integrase

Journal of Molecular Biology
Srisunder SubramaniamMark P Foster

Abstract

Bacteriophage lambda integrase (lambda-Int) is the prototypical member of a large family of enzymes that catalyze site-specific DNA recombination via the formation of a Holliday junction intermediate. DNA strand cleavage by lambda-Int is mediated by nucleophilic attack on the scissile phosphate by a conserved tyrosine residue, forming an intermediate with the enzyme covalently attached to the 3'-end of the cleaved strand via a phosphotyrosine linkage. The crystal structure of the catalytic domain of lambda-Int (C170) obtained in the absence of DNA revealed the tyrosine nucleophile at the protein's C terminus to be located on a beta-hairpin far from the other conserved catalytic residues and adjacent to a disordered loop. This observation suggested that a conformational change in the C terminus of the protein was required to generate the active site in cis, or alternatively, that the active site could be completed in trans by donation of the tyrosine nucleophile from a neighboring molecule in the recombining synapse. We used NMR spectroscopy together with limited proteolysis to examine the dynamics of the lambda-Int catalytic domain in the presence and absence of DNA half-site substrates with the goal of characterizing the expec...Continue Reading

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Citations

Jun 10, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Hari B KamaduraiMark P Foster
Jun 8, 2006·Annual Review of Biochemistry·Nigel D F GrindleyPhoebe A Rice
Jan 19, 2016·Journal of Molecular Biology·Paris LadiasIoannis Georgiou
Mar 20, 2015·Protein Engineering, Design & Selection : PEDS·Jia Wei SiauFarid J Ghadessy
Apr 1, 2006·Journal of Molecular Recognition : JMR·Patricia A KhuuP Shing Ho
Jul 10, 2003·The Journal of Biological Chemistry·Linda Lee, Paul D Sadowski
Oct 18, 2003·The Journal of Biological Chemistry·Franklin A HaysP Shing Ho
Sep 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Aparna UnnikrishnanMark P Foster

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