PDBsum entry 3vtk

Transferase

PDB id: 3vtk

Contents

Protein chain

313 a.a. *

Ligands

ADP

5IU

Waters ×6

* Residue conservation analysis

PDB id:

3vtk

Name:

Transferase

Title:

Thymidine kinase from herpes simplex virus type 1 in complex with adp and 5-iodo-deoxyuridine-monophosphate

Structure:

Thymidine kinase. Chain: a. Engineered: yes

Source:

Herpes simplex virus (type 1 / strain f). Organism_taxid: 10304. Strain: f. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Homo-Dimer (from PDB file)

Resolution:

3.00Å R-factor: 0.222 R-free: 0.305

Authors:

K.Wild,G.E.Schulz

Key ref:

K.Wild et al. (1997). The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue. Protein Sci, 6, 2097-2106. PubMed id: 9336833 DOI: 10.1002/pro.5560061005

Date:

01-Apr-97 Release date: 22-Oct-97

Protein chain

P0DTH5  (KITH_HHV11) -  Thymidine kinase from Human herpesvirus 1 (strain 17)

Seq: 376 a.a.

Struc: 313 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.1.21 - thymidine kinase.
• Reaction: thymidine + ATP = dTMP + ADP + H⁺

thymidine + ATP = dTMP (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP (Bound ligand (Het Group name = 5IU) matches with 90.91% similarity) + H(+)

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

reference

DOI no: 10.1002/pro.5560061005

Protein Sci 6:2097-2106 (1997)

PubMed id: 9336833

The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue.

K.Wild, T.Bohner, G.Folkers, G.E.Schulz.

ABSTRACT

Thymidine kinase from Herpes simplex virus type 1 (TK) was crystallized in an N-terminally truncated but fully active form. The structures of TK complexed with ADP at the ATP-site and deoxythymidine-5'-monophosphate (dTMP), deoxythymidine (dT), or idoxuridine-5'-phosphate (5-iodo-dUMP) at the substrate-site were refined to 2.75 A, 2.8 A, and 3.0 A resolution, respectively. TK catalyzes the phosphorylation of dT resulting in an ester, and the phosphorylation of dTMP giving rise to an anhydride. The presented TK structures indicate that there are only small differences between these two modes of action. Glu83 serves as a general base in the ester reaction. Arg163 parks at an internal aspartate during ester formation and binds the alpha-phosphate of dTMP during anhydride formation. The bound deoxythymidine leaves a 35 A3 cavity at position 5 of the base and two sequestered water molecules at position 2. Cavity and water molecules reduce the substrate specificity to such an extent that TK can phosphorylate various substrate analogues useful in pharmaceutical applications. TK is structurally homologous to the well-known nucleoside monophosphate kinases but contains large additional peptide segments.

Selected figure(s)

Figure 1.
ig. 1. Stereoviewofthesymmetric TK dimerwithboundADPanddTMP.Thedomainsaredefinedaccording to theNMP-kinases asCORE(residues 46-81,143-218.227-250.323-376, yellow, Wbi n,j (82-142, red), and ID (219-226, blue).The 72 additional residuesaroundosition 90 are green.Mobileparts are givenasdashedlines,thetwofold axis is inserted,secondary structures are defined in Fig. 2.

Figure 3.
Fig. 3. Final (2F0 - F,)-electron density maps or all substrates with the C trace of the P-loop as reference. All maps are contoured at the .0 (T level. A: ADPanddTPat 8, B: ADP and dTat 2.8 8, resolution. C: ADPand at 3.0 8, resolution.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1997, 6, 2097-2106) copyright 1997.

Figures were selected by an automated process.