Disease relevance of Mup03

• Primary structure of phage mu transposase: homology to mu repressor [1].
• The phosphorothioate stereoselectivity of the corresponding steps of phage Mu transposition and HIV DNA integration matches that of Tn10 reaction, indicating a common mode of substrate-active site interactions for this class of DNA transposition reactions [2].
• ClpX protein of Escherichia coli activates bacteriophage Mu transposase in the strand transfer complex for initiation of Mu DNA synthesis [3].
• The wing of the enhancer-binding domain of Mu phage transposase is flexible and is essential for efficient transposition [4].
• Thus, Tn552 encodes: (i) resL-binL, a co-integrate resolution system homologous with those of Tn3 family elements; (ii) p480, a potential transposase significantly homologous with the DNA integrases of eukaryotic retroviruses and retrotransposons; and (iii) p271, a potential ATP-binding protein that shows homology with the B protein of phage Mu [5].

High impact information on Mup03

• Path of DNA within the Mu transpososome. Transposase interactions bridging two Mu ends and the enhancer trap five DNA supercoils [6].
• For Tn10 and phage Mu, a single active site of one transposase protomer catalyzes the successive transposition reaction steps [2].
• We examined phosphorothioate stereoselectivity at the scissile position for all four reaction steps catalyzed by the Tn10 transposase [2].
• The transposase family of proteins mediate DNA transposition or retroviral DNA integration via multistep phosphoryl transfer reactions [2].
• The interwoven architecture of the Mu transposase couples DNA synapsis to catalysis [7].

Chemical compound and disease context of Mup03

• The NH2 terminus of the Mu transposase has considerable sequence homology with the Mu repressor and with the NH2 terminus of the transposase of the Mu-like phage D108 [1].
• A bipartite enhancer sequence (composed of the O1 and O2 operator sites) is essential for assembly of the functional tetramer of phage Mu transposase (MuA) on supercoiled DNA substrates [8].

Biological context of Mup03

• We present the complete nucleotide and derived amino acid sequence of the transposase and analyze implications for transposase/DNA interaction [1].
• We propose that the connections between the two subdomains may be involved in the cross-talk between the active site and the other domains of the transposase that controls the activity of the protein [9].
• The mutant transposase was indistinguishable from wild-type Mu A in binding affinity for both the Mu ends and the enhancer, and in strand transfer activity when the cleavage step was bypassed [10].
• The phage Mu transposase (MuA) binds to the ends of the Mu genome during the assembly of higher order nucleoprotein complexes [11].
• A novel DNA binding and nuclease activity in domain III of Mu transposase: evidence for a catalytic region involved in donor cleavage [10].

Associations of Mup03 with chemical compounds

• This active site uses all three DDE residues from the subunit bound to the transposase binding site proximal to the cleavage site on the other Mu DNA end (catalysis in trans) [12].
• The right operator, O2, shows a preferential interaction with the transposase subunit at the L1 site (within the left att sequence) that is responsible for cleaving the right end of Mu [8].
• Hydroxyl radical footprints show that the transposase binds to one face of the DNA helix and covers two consecutive major grooves [13].
• The effect of the tyrosine substitutions is specific for target interaction as both mutants show wild-type activity in their ability to stimulate the Mu transposase to perform donor cleavage and intramolecular strand transfer [14].
• Tyrosine 414 may reside within an important, yet non-essential, site of transposase, as an aspartate-substituted protein had a drastically reduced frequency of transposition, while the remaining mutants yielded reduced, but substantial, frequencies of microMu transposition in vivo [15].

Analytical, diagnostic and therapeutic context of Mup03

• Electron spectroscopic imaging (ESI) of the DNA-phosphorus was performed in conjunction with the structural investigation to derive the path of the DNA through the transpososome and to define the DNA-binding surface in the transposase [16].
• The dissection of the functional domains of the related phage Mu and D108 transposase proteins will provide clues to the mechanisms and evolution of DNA transposition as a mode of mobile genetic element propagation [17].

References