TY - JOUR
T1 - Crystal structure of the amino-terminal fragment of vaccinia virus DNA topoisomerase I at 1.6 å resolution
AU - Sharma, Amit
AU - Hanai, Ryo
AU - Mondragón, Alfonso
PY - 1994/8
Y1 - 1994/8
N2 - Background Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. Results The crystal structure of a 9kDa amino terminal fragment of vaccinia virus DNA topoisomerase I has been determined at 1.6 å resolution. The fragment forms a five-stranded, anti-parallel β -sheet with two short α-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure. Conclusions This is the first atomic structure of any region of a eukaryotic-like DNA topoisomerase I. It has provided insights into the structural bases of the phenotypes of some single-site mutants of the intact topoisomerase. The structure has enabled us to study the interactions within a well-folded protein fragment. and the camptothecin resistance of the viral topoisomerase.
AB - Background Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. Results The crystal structure of a 9kDa amino terminal fragment of vaccinia virus DNA topoisomerase I has been determined at 1.6 å resolution. The fragment forms a five-stranded, anti-parallel β -sheet with two short α-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure. Conclusions This is the first atomic structure of any region of a eukaryotic-like DNA topoisomerase I. It has provided insights into the structural bases of the phenotypes of some single-site mutants of the intact topoisomerase. The structure has enabled us to study the interactions within a well-folded protein fragment. and the camptothecin resistance of the viral topoisomerase.
KW - Amino terminal fragment
KW - Vaccinia virus DNA topoisomerase I
KW - X-ray structure
KW - eukaryotic topoisomerases
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U2 - 10.1016/S0969-2126(94)00077-8
DO - 10.1016/S0969-2126(94)00077-8
M3 - Article
C2 - 7994576
AN - SCOPUS:0028774040
SN - 0969-2126
VL - 2
SP - 767
EP - 777
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 8
ER -