PDBsum entry 1mzc

Transferase

PDB id: 1mzc

Contents

Protein chains

313 a.a. *

407 a.a. *

Ligands

GLC-FRU

FPP

BNE

Metals

_ZN

Waters ×703

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Dual protein farnesyltransferase-Geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents.
• Authors: S.J.Desolms, T.M.Ciccarone, S.C.Mactough, A.W.Shaw, C.A.Buser, M.Ellis-Hutchings, C.Fernandes, K.A.Hamilton, H.E.Huber, N.E.Kohl, R.B.Lobell, R.G.Robinson, N.N.Tsou, E.S.Walsh, S.L.Graham, L.S.Beese, J.S.Taylor.
• Ref.: J Med Chem, 2003, 46, 2973-2984. [DOI no: 10.1021/jm020587n]
• PubMed id: 12825937

Abstract

A series of novel diaryl ether lactams have been identified as very potent dual inhibitors of protein farnesyltransferase (FTase) and protein geranylgeranyltransferase I (GGTase-I), enzymes involved in the prenylation of Ras. The structure of the complex formed between one of these compounds and FTase has been determined by X-ray crystallography. These compounds are the first reported to inhibit the prenylation of the important oncogene Ki-Ras4B in vivo. Unfortunately, doses sufficient to achieve this endpoint were rapidly lethal.