1XBT

Crystal Structure of Human Thymidine Kinase 1

Summary for 1XBT

• Entry DOI: 10.2210/pdb1xbt/pdb
• Descriptor: Thymidine kinase, cytosolic, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: deoxyribonucleoside kinase, zinc-binding domain, feedback inhibitor, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P04183
• Total number of polymer chains: 8
• Total formula weight: 175191.06

Authors

Welin, M.,Kosinska, U.,Mikkelsen, N.E.,Carnrot, C.,Zhu, C.,Wang, L.,Eriksson, S.,Munch-Petersen, B.,Eklund, H. (deposition date: 2004-08-31, release date: 2004-12-14, Last modification date: 2024-03-13)

Primary citation

Welin, M.,Kosinska, U.,Mikkelsen, N.E.,Carnrot, C.,Zhu, C.,Wang, L.,Eriksson, S.,Munch-Petersen, B.,Eklund, H.
Structures of thymidine kinase 1 of human and mycoplasmic origin
Proc.Natl.Acad.Sci.Usa, 101:17970-17975, 2004

PubMed Abstract: 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.

PubMed: 15611477
DOI: 10.1073/pnas.0406332102

Experimental method

X-RAY DIFFRACTION (2.4 Å)