PDBsum entry: 1tn7

Transferase

PDB id: 1tn7

Contents

Protein chains

323 a.a. *

407 a.a. *

Ligands

THR-LYS-CYS-VAL-ILE-PHE

ACY ×2

FII

Metals

_ZN

Waters ×357

* Residue conservation analysis

PDB id:

1tn7

Name:

Transferase

Title:

Protein farnesyltransferase complexed with a tc21 peptide substrate and a fpp analog at 2.3a resolution

Structure:

Protein farnesyltransferase alpha subunit. Chain: a. Synonym: caax farnesyltransferase alpha subunit, ftase- alpha. Engineered: yes. Protein farnesyltransferase beta subunit. Chain: b. Synonym: caax farnesyltransferase beta subunit, ftase-beta. Engineered: yes.

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: fnta. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: fntb. Synthetic: yes. Other_details: the fusion protein was chemically

Biol. unit:

Trimer (from PQS)

Resolution:

2.30Å R-factor: 0.180 R-free: 0.207

Authors:

T.S.Reid,K.L.Terry,P.J.Casey,L.S.Beese

Key ref:

T.S.Reid et al. (2004). Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J Mol Biol, 343, 417-433. PubMed id: 15451670 DOI: 10.1016/j.jmb.2004.08.056

Date:

11-Jun-04 Release date: 02-Nov-04

Protein chain

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

Seq: 377 a.a.

Struc: 323 a.a.

Protein chain

Q02293  (FNTB_RAT) -  Protein farnesyltransferase subunit beta

Seq: 437 a.a.

Struc: 407 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 = FII) matches with 50.00% 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 = FII) matches with 43.00% 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 (4 terms)
• Biological process: response to inorganic substance (15 terms)
• Biochemical function: catalytic activity (14 terms)

reference

DOI no: 10.1016/j.jmb.2004.08.056

J Mol Biol 343:417-433 (2004)

PubMed id: 15451670

Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity.

T.S.Reid, K.L.Terry, P.J.Casey, L.S.Beese.

ABSTRACT

Post-translational modifications are essential for the proper function of many proteins in the cell. The attachment of an isoprenoid lipid (a process termed prenylation) by protein farnesyltransferase (FTase) or geranylgeranyltransferase type I (GGTase-I) is essential for the function of many signal transduction proteins involved in growth, differentiation, and oncogenesis. FTase and GGTase-I (also called the CaaX prenyltransferases) recognize protein substrates with a C-terminal tetrapeptide recognition motif called the Ca1a2X box. These enzymes possess distinct but overlapping protein substrate specificity that is determined primarily by the sequence identity of the Ca1a2X motif. To determine how the identity of the Ca1a2X motif residues and sequence upstream of this motif affect substrate binding, we have solved crystal structures of FTase and GGTase-I complexed with a total of eight cognate and cross-reactive substrate peptides, including those derived from the C termini of the oncoproteins K-Ras4B, H-Ras and TC21. These structures suggest that all peptide substrates adopt a common binding mode in the FTase and GGTase-I active site. Unexpectedly, while the X residue of the Ca1a2X motif binds in the same location for all GGTase-I substrates, the X residue of FTase substrates can bind in one of two different sites. Together, these structures outline a series of rules that govern substrate peptide selectivity; these rules were utilized to classify known protein substrates of CaaX prenyltransferases and to generate a list of hypothetical substrates within the human genome.

Selected figure(s)

Figure 1.
Figure 1. Chemical structures of isoprenoid diphosphates and non-hydrolyzable analogs.

Figure 4.
Figure 4. Comparison of the a[2] binding site in FTase and GGTase-I. Superposition of FTase and GGTase-I shows residues that interact with the a[2] residue of the Ca[1]a[2]X motif. Regions of the FTase ternary complex forming the a[2] binding site (enzyme residues Trp102b, Trp106b and Tyr361b and isoprene 3) are colored red. Corresponding regions of the GGTase-I ternary complex (enzyme residues Thr49b, Phe53b and Leu321b, isoprenes 3 and 4, and substrate peptide X residue) are colored blue. Portions of the FPP and GGPP analogs (gray) and of the CVIM (pink) and CVIL (light blue) peptides not forming the a[2] site are shown.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 343, 417-433) copyright 2004.

Figures were selected by the author.