PDBsum entry 2f0y

Transferase

PDB id: 2f0y

Contents

Protein chains

314 a.a. *

395 a.a. *

Ligands

FPP

3MN

Metals

_ZN

Waters ×409

* Residue conservation analysis

PDB id:

2f0y

Name:

Transferase

Title:

Crystal structure of human protein farnesyltransferase complexed with farnesyl diphosphate and hydantoin derivative

Structure:

Protein farnesyltransferase/geranylgeranyltransferase type i alpha subunit. Chain: a. Synonym: caax farnesyltransferase alpha subunit, ras proteins prenyltransferase alpha, ftase-alpha, type i protein geranyl- geranyltransferase alpha subunit, ggtase-i-alpha. Engineered: yes. Protein farnesyltransferase beta subunit. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.70Å R-factor: 0.212 R-free: 0.258

Authors:

K.H.Kim,J.Lee,J.Kim

Key ref:

J.Lee et al. (2006). Hydantoin derivatives as non-peptidic inhibitors of Ras farnesyl transferase. Bioorg Med Chem Lett, 16, 1954-1956. PubMed id: 16442288

Date:

14-Nov-05 Release date: 14-Nov-06

Protein chain

P49354  (FNTA_HUMAN) -  Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha from Homo sapiens

Seq: 379 a.a.

Struc: 314 a.a.

Protein chain

P49356  (FNTB_HUMAN) -  Protein farnesyltransferase subunit beta from Homo sapiens

Seq: 437 a.a.

Struc: 395 a.a.

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.2.5.1.58 - protein farnesyltransferase.
• Reaction: L-cysteinyl-[protein] + (2E,6E)-farnesyl diphosphate = S-(2E,6E)- farnesyl-L-cysteinyl-[protein] + diphosphate

L-cysteinyl-[protein] (Bound ligand (Het Group name = FPP) corresponds exactly) + (2E,6E)-farnesyl diphosphate = S-(2E,6E)- farnesyl-L-cysteinyl-[protein] + diphosphate

• Cofactor: Mg(2+); Zn(2+)
• Enzyme class 2: Chain A: E.C.2.5.1.59 - protein geranylgeranyltransferase type I.
• Reaction: geranylgeranyl diphosphate + L-cysteinyl-[protein] = S-geranylgeranyl-L- cysteinyl-[protein] + diphosphate

geranylgeranyl diphosphate (Bound ligand (Het Group name = FPP) matches with 82.76% similarity) + L-cysteinyl-[protein] = S-geranylgeranyl-L- cysteinyl-[protein] + diphosphate

• Cofactor: Zn(2+)

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

reference

Bioorg Med Chem Lett 16:1954-1956 (2006)

PubMed id: 16442288

Hydantoin derivatives as non-peptidic inhibitors of Ras farnesyl transferase.

J.Lee, J.Kim, J.S.Koh, H.H.Chung, K.H.Kim.

ABSTRACT

1,3,5,5-Tetrasubstituted 2,4-imidazolinedione (hydantoin) derivatives were evaluated as Ftase inhibitors. Potent Ftase inhibitors without thiol or peptide were obtained in three steps.