PDBsum entry: 1n94

Transferase

PDB id: 1n94

Contents

Protein chains

315 a.a. *

397 a.a. *

Ligands

HFP

TIN

Metals

_ZN

* Residue conservation analysis

PDB id:

1n94

Name:

Transferase

Title:

Aryl tetrahydropyridine inhbitors of farnesyltransferase: glycine, phenylalanine and histidine derivates

Structure:

Protein farnesyltransferase alpha subunit. Chain: a. Fragment: residues 55-369. Synonym: caax farnesyl transferase alpha subunit, ras proteins prenyltransferase alpha, ftase-alpha. Engineered: yes. Protein farnesyltransferase beta subunit. Chain: b. Fragment: residues 22-418.

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Biol. unit:

Dimer (from PQS)

Resolution:

3.50Å R-factor: 0.295 R-free: 0.296

Authors:

S.L.Gwaltney Ii,S.J.O'Connor,L.T.Nelson,G.M.Sullivan, H.Imade,W.Wang,L.Hasvold,Q.Li,J.Cohen,W.Z.Gu

Key ref:

S.L.Gwaltney et al. (2003). Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives. Bioorg Med Chem Lett, 13, 1359-1362. PubMed id: 12657282 DOI: 10.1016/S0960-894X(03)00095-7

Date:

22-Nov-02 Release date: 07-Jan-03

Protein chain

Q04631  (FNTA_RAT) -  Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha

Seq: 377 a.a.

Struc: 315 a.a.

Protein chain

Q02293  (FNTB_RAT) -  Protein farnesyltransferase subunit beta

Seq: 437 a.a.

Struc: 397 a.a.

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.2.5.1.58 - Protein farnesyltransferase.
• Reaction: Farnesyl diphosphate + protein-cysteine = S-farnesyl protein + diphosphate

Farnesyl diphosphate (Bound ligand (Het Group name = HFP) matches with 57.00% similarity) + protein-cysteine = S-farnesyl protein + diphosphate

• Cofactor: Magnesium; Zinc
• Enzyme class 2: Chain A: E.C.2.5.1.59 - Protein geranylgeranyltransferase type I.
• Reaction: Geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl- protein + diphosphate

Geranylgeranyl diphosphate (Bound ligand (Het Group name = HFP) matches with 48.00% similarity) + protein-cysteine = S-geranylgeranyl- protein + diphosphate

• Cofactor: Zinc

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

 Gene Ontology (GO) functional annotation 

• Cellular component: protein complex (2 terms)
• Biological process: response to inorganic substance (11 terms)
• Biochemical function: catalytic activity (12 terms)

reference

DOI no: 10.1016/S0960-894X(03)00095-7

Bioorg Med Chem Lett 13:1359-1362 (2003)

PubMed id: 12657282

Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives.

S.L.Gwaltney, S.J.O'Connor, L.T.Nelson, G.M.Sullivan, H.Imade, W.Wang, L.Hasvold, Q.Li, J.Cohen, W.Z.Gu, S.K.Tahir, J.Bauch, K.Marsh, S.C.Ng, D.J.Frost, H.Zhang, S.Muchmore, C.G.Jakob, V.Stoll, C.Hutchins, S.H.Rosenberg, H.L.Sham.

ABSTRACT

Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered a series of aryl tetrahydropyridines that incorporate substituted glycine, phenylalanine and histidine residues. The design, synthesis, SAR and biological properties of these compounds will be discussed.