PDBsum entry 1p7c

Transferase

PDB id: 1p7c

Contents

Protein chains

301 a.a. *

318 a.a. *

Ligands

T5A

SO4

THM

Waters ×340

* Residue conservation analysis

PDB id:

1p7c

Name:

Transferase

Title:

Crystal structure of hsv1-tk complexed with tp5a

Structure:

Thymidine kinase. Chain: a, b. Engineered: yes

Source:

Herpes simplex virus (type 1 / strain 17). Organism_taxid: 10299. Strain: 17. Gene: tk or ul23. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.244 R-free: 0.285

Authors:

A.Gardberg,L.Shuvalova,C.Monnerjahn,M.Konrad,A.Lavie

Key ref:

A.Gardberg et al. (2003). Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases. Structure, 11, 1265-1277. PubMed id: 14527394 DOI: 10.1016/j.str.2003.09.003

Date:

01-May-03 Release date: 04-Nov-03

Protein chain

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

Seq: 376 a.a.

Struc: 301 a.a.*

Protein chain

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

Seq: 376 a.a.

Struc: 318 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

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

thymidine (Bound ligand (Het Group name = T5A) matches with 56.36% similarity) + ATP (Bound ligand (Het Group name = THM) corresponds exactly) = dTMP + ADP + H(+)

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

reference

DOI no: 10.1016/j.str.2003.09.003

Structure 11:1265-1277 (2003)

PubMed id: 14527394

Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases.

A.Gardberg, L.Shuvalova, C.Monnerjahn, M.Konrad, A.Lavie.

ABSTRACT

Crystal structures of equine herpesvirus type-4 thymidine kinase (EHV4-TK) in complex with (i). thymidine and ADP, (ii). thymidine and SO(4) and the bisubstrate analogs, (iii). TP(4)A, and (iv). TP(5)A have been solved. Additionally, the structure of herpes simplex virus type-1 thymidine kinase (HSV1-TK) in complex with TP(5)A has been determined. These are the first structures of nucleoside kinases revealing conformational transitions upon binding of bisubstrate analogs. The structural basis for the dual thymidine and thymidylate kinase activity of these TKs is elucidated. While the active sites of HSV1-TK and EHV4-TK resemble one another, notable differences are observed in the Lid regions and in the way the enzymes bind the base of the phosphoryl-acceptor. The latter difference could partly explain the higher activity of EHV4-TK toward the prodrug ganciclovir.

Selected figure(s)

Figure 2.
Figure 2. Schematic Diagram Showing the Interactions Made by TP[4]A and TP[5]ADue to the all-open Lid conformations in the EHV4-TK TP[4]A and TP[5]A complex structures (but closed in the HSV1-TK structure), in (A) and (B) we modeled the closed-Lid conformation as observed in the EHV4-TK/ADP-Thy complex (simulated contacts shown in red and marked with an asterisk).(A) EHV4-TK complexed with TP[4]A. Owing to the 0.4 Å displacement of the b-phosphate, there is only one hydrogen bond to the P loop.(B) EHV4-TK complexed with TP[5]A, where only the mechanistically relevant conformation is shown.(C) HSV1-TK complexed with TP[5]A.

The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 1265-1277) copyright 2003.

Figure was selected by an automated process.