1P7C

Crystal Structure of HSV1-TK complexed with TP5A

Summary for 1P7C

• Entry DOI: 10.2210/pdb1p7c/pdb
• Related: 1P6X 1P72 1P73 1P75
• Descriptor: Thymidine kinase, P1-(5'-ADENOSYL)P5-(5'-THYMIDYL)PENTAPHOSPHATE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: p-loop, lid, bisubstrate inhibitor, transferase
• Biological source: Herpes simplex virus (type 1 / strain 17)
• Total number of polymer chains: 2
• Total formula weight: 75640.86

Authors

Gardberg, A.,Shuvalova, L.,Monnerjahn, C.,Konrad, M.,Lavie, A. (deposition date: 2003-05-01, release date: 2003-11-04, Last modification date: 2023-08-16)

Primary citation

Gardberg, A.,Shuvalova, L.,Monnerjahn, C.,Konrad, M.,Lavie, A.
Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases.
Structure, 11:1265-1277, 2003

PubMed 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.

PubMed: 14527394
DOI: 10.1016/j.str.2003.09.003

Experimental method

X-RAY DIFFRACTION (2.1 Å)