1xbt

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1xbt, resolution 2.40Å

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Crystal Structure of Human Thymidine Kinase 1

Overview

Cytosolic thymidine kinase 1, TK1, is a well known cell-cycle-regulated, enzyme of importance in nucleotide metabolism as well as an activator of, antiviral and anticancer drugs such as 3'-azido-3'-deoxythymidine (AZT)., We have now determined the structures of the TK1 family, the human and, Ureaplasma urealyticum enzymes, in complex with the feedback inhibitor, dTTP. The TK1s have a tetrameric structure in which each subunit contains, an alpha/beta-domain that is similar to ATPase domains of members of the, RecA structural family and a domain containing a structural zinc. The zinc, ion connects beta-structures at the root of a beta-ribbon that forms a, stem that widens to a lasso-type loop. The thymidine of dTTP is, hydrogen-bonded to main-chain atoms predominantly coming from the lasso, loop. This binding is in contrast to other deoxyribonucleoside kinases, where specific interactions occur with side chains. The TK1 structure, differs fundamentally from the structures of the other deoxyribonucleoside, kinases, indicating a different evolutionary origin.

About this Structure

1XBT is a Single protein structure of sequence from Homo sapiens with ZN, MG and TTP as ligands. Active as Thymidine kinase, with EC number 2.7.1.21 Full crystallographic information is available from OCA.

Reference

Structures of thymidine kinase 1 of human and mycoplasmic origin., Welin M, Kosinska U, Mikkelsen NE, Carnrot C, Zhu C, Wang L, Eriksson S, Munch-Petersen B, Eklund H, Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):17970-5. Epub 2004 Dec 20. PMID:15611477

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