TY - JOUR
T1 - Similarities and differences among 105 members of the Int family of site-specific recombinases
AU - Nunes-Düby, Simone E.
AU - Kwon, Hyock Joo
AU - Tirumalai, Radhakrishna S.
AU - Ellenberger, Tom
AU - Landy, Arthur
N1 - Funding Information:
We thank Drs D.J.Sherratt, D.B.Wigley, G.D.van Dyne, M.Jayaram, J.W.Golden, L.Dijkhuizen, P.Roy, J.Eriksson and E.Haggård for communicating data before publication. We thank Jeffrey C.Liu for computer programming and Joan Boyles for help with preparation of the manuscript. This work was supported by NIST grant 60NANB5D0009 (S.E.N.-D.), a Howard Hughes Medical Institute Predoctoral Fellowship (H.J.K.), the Lucille P.Markey Charitable Trust (T.E.E.) and NIH grants AI13544 and GM33928 (A.L.).
PY - 1998/1/15
Y1 - 1998/1/15
N2 - Alignments of 105 site-specific recombinases belonging to the Int family of proteins identified extended areas of similarity and three types of structural differences. In addition to the previously recognized conservation of the tetrad R-H-R-Y, located in boxes I and II, several newly identified sequence patches include charged amino acids that are highly conserved and a specific pattern of buried residues contributing to the overall protein fold. With some notable exceptions, unconserved regions correspond to loops in the crystal structures of the catalytic domains of λ Int (Int c170) and HP1 Int (HPC) and of the recombinases XerD and Cre. Two structured regions also harbor some pronounced differences. The first comprises β-sheets 4 and 5, α-helix D and the adjacent loop connecting it to α-helix E: two Ints of phages infecting thermophilic bacteria are missing this region altogether; the crystal structures of HPC, XerD and Cre reveal a lack of β-sheets 4 and 5; Cre displays two additional β-sheets following α-helix D; five recombinases carry large insertions. The second involves the catalytic tyrosine and is seen in a comparison of the four crystal structures. The yeast recombinases can theoretically be fitted to the Int fold, but the overall differences, involving changes in spacing as well as in motif structure, are more substantial than seen in most other proteins. The phenotypes of mutations compiled from several proteins are correlated with the available structural information and structure-function relationships are discussed. In addition, a few prokaryotic and eukaryotic enzymes with partial homology with the Int family of recombinases may be distantly related, either through divergent or convergent evolution. These include a restriction enzyme and a subgroup of eukaryotic RNA helicases (D-E-A-D proteins).
AB - Alignments of 105 site-specific recombinases belonging to the Int family of proteins identified extended areas of similarity and three types of structural differences. In addition to the previously recognized conservation of the tetrad R-H-R-Y, located in boxes I and II, several newly identified sequence patches include charged amino acids that are highly conserved and a specific pattern of buried residues contributing to the overall protein fold. With some notable exceptions, unconserved regions correspond to loops in the crystal structures of the catalytic domains of λ Int (Int c170) and HP1 Int (HPC) and of the recombinases XerD and Cre. Two structured regions also harbor some pronounced differences. The first comprises β-sheets 4 and 5, α-helix D and the adjacent loop connecting it to α-helix E: two Ints of phages infecting thermophilic bacteria are missing this region altogether; the crystal structures of HPC, XerD and Cre reveal a lack of β-sheets 4 and 5; Cre displays two additional β-sheets following α-helix D; five recombinases carry large insertions. The second involves the catalytic tyrosine and is seen in a comparison of the four crystal structures. The yeast recombinases can theoretically be fitted to the Int fold, but the overall differences, involving changes in spacing as well as in motif structure, are more substantial than seen in most other proteins. The phenotypes of mutations compiled from several proteins are correlated with the available structural information and structure-function relationships are discussed. In addition, a few prokaryotic and eukaryotic enzymes with partial homology with the Int family of recombinases may be distantly related, either through divergent or convergent evolution. These include a restriction enzyme and a subgroup of eukaryotic RNA helicases (D-E-A-D proteins).
UR - http://www.scopus.com/inward/record.url?scp=0038659759&partnerID=8YFLogxK
U2 - 10.1093/nar/26.2.391
DO - 10.1093/nar/26.2.391
M3 - Article
C2 - 9421491
AN - SCOPUS:0038659759
SN - 0305-1048
VL - 26
SP - 391
EP - 406
JO - Nucleic acids research
JF - Nucleic acids research
IS - 2
ER -