Author/Editor		Johansson, Kenth; Ramaswamy, S; Ljungcrantz, Catarina; Knecht, Wolfgang; Piškur, Jure; Munch-Petersen, Birgitte; Eriksson, Staffan; Eklund, Hans
Title		Structural basis for substrate specificities of cellular deoxyribonucleoside kinases
Type		članek
Source		Nat Struct Biol
Vol. and No.		Letnik 8, št. 7
Publication year		2001
Volume		str. 616-20
Language		eng
Abstract		Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases.
Descriptors		ADENOSINE TRIPHOSPHATE AMINO ACID SEQUENCE ANIMALS BINDING SITES CRYSTALLOGRAPHY, X-RAY DEOXYCYTIDINE DROSOPHILA MELANOGASTER HYDROGEN BONDING MODELS, MOLECULAR MOLECULAR SEQUENCE DATA PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR) PROTEIN CONFORMATION SEQUENCE ALIGNMENT STRUCTURE-ACTIVITY RELATIONSHIP SUBSTRATE SPECIFICITY