PDBsum entry 1w4r

Transferase

PDB id: 1w4r

Contents

Protein chains

174 a.a. *

(+ 0 more) 160 a.a. *

Ligands

TTP ×8

DTU

Metals

_ZN ×8

Waters ×794

* Residue conservation analysis

PDB id:

1w4r

Name:

Transferase

Title:

Structure of a type ii thymidine kinase with bound dttp

Structure:

Thymidine kinase. Chain: a, b, c, d, e, f, g, h. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.83Å R-factor: 0.160 R-free: 0.189

Authors:

M.S.Birringer,M.T.Claus,G.Folkers,D.P.Kloer,G.E.Schulz,L.Scapozza

Key ref:

M.S.Birringer et al. (2005). Structure of a type II thymidine kinase with bound dTTP. FEBS Lett, 579, 1376-1382. PubMed id: 15733844 DOI: 10.1016/j.febslet.2005.01.034

Date:

27-Jul-04 Release date: 01-Feb-05

Protein chains

P04183  (KITH_HUMAN) -  Thymidine kinase, cytosolic from Homo sapiens

Seq: 234 a.a.

Struc: 174 a.a.

Protein chains

P04183  (KITH_HUMAN) -  Thymidine kinase, cytosolic from Homo sapiens

Seq: 234 a.a.

Struc: 160 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.2.7.1.21 - thymidine kinase.
• Reaction: thymidine + ATP = dTMP + ADP + H⁺

thymidine + ATP (Bound ligand (Het Group name = TTP) matches with 76.47% similarity) = dTMP + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.febslet.2005.01.034

FEBS Lett 579:1376-1382 (2005)

PubMed id: 15733844

Structure of a type II thymidine kinase with bound dTTP.

M.S.Birringer, M.T.Claus, G.Folkers, D.P.Kloer, G.E.Schulz, L.Scapozza.

ABSTRACT

The structure of human cytosolic thymidine kinase in complex with its feedback inhibitor 2'-deoxythymidine-5'-triphosphate was determined. This structure is the first representative of the type II thymidine kinases found in several pathogens. The structure deviates strongly from the known structures of type I thymidine kinases such as the Herpes simplex enzyme. It contains a zinc-binding domain with four cysteines complexing a structural zinc ion. Interestingly, the backbone atoms of the type II enzyme bind thymine via hydrogen-bonds, in contrast to type I, where side chains are involved. This results in a specificity difference exploited for antiviral therapy. The presented structure will foster the development of new drugs and prodrugs for numerous therapeutic applications.

Selected figure(s)

Figure 3.
Fig. 3. Stereoview of the active center of hTK1. Water molecules are red balls, hydrogen bonds are dashed lines. (A) Bound feedback inhibitor dTTP with hydrogen bonding network. The conformation of dTTP in its two binding modes was derived from the F[o]–F[c] omit electron density map here contoured at 3σ (green). The 40% binding mode is shown in a semi transparent mode. (B) The nucleotide is bound by the tight interactions with protein residues. Hydrogen bonds to main chain atoms and stacking of the pyrimidine ring between Phe101, Phe133 and Tyr181 are responsible for the high substrate specificity.

Figure 4.
Fig. 4. B-factor plot of the eight subunits of the reported hTK1 structure. The map correlation is depicted on the right side of the diagram. High mobility of some residues leads to lacking parts in the structure. The line on top shows the secondary structure assignment as given by the program DSSP [20]. The β-sheets and helices are displayed as arrows and tubes, respectively and labeled.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2005, 579, 1376-1382) copyright 2005.

Figures were selected by an automated process.