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PDBsum entry 1fpp
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protein ligands metals Protein-protein interface(s) links
Prenyltransferase PDB id
1fpp

 

 

 

 

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Contents
Protein chains
400 a.a. *
316 a.a. *
Ligands
PO4
FPP
Metals
_ZN
Waters ×17
* Residue conservation analysis
PDB id:
1fpp
Name: Prenyltransferase
Title: Protein farnesyltransferase complex with farnesyl diphosphate
Structure: Protein farnesyltransferase. Chain: b. Synonym: ftase. Engineered: yes. Other_details: purified recombinant ftase was treated with protease gluc prior to crystallization. Protein farnesyltransferase. Chain: a. Synonym: ftase.
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: fnta, fntb. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five (invitrogen). Other_details: viral expression constructs were provided by m. S. Brown and j. L. Goldstein (southwestern medical center, dallas, tx).
Biol. unit: Hetero-Dimer (from PDB file)
Resolution:
2.75Å     R-factor:   0.240     R-free:   0.300
Authors: P.Dunten,U.Kammlott,R.Crowther,D.Weber,R.Palermo,J.Birktoft
Key ref: P.Dunten et al. (1998). Protein farnesyltransferase: structure and implications for substrate binding. Biochemistry, 37, 7907-7912. PubMed id: 9609683 DOI: 10.1021/bi980531o
Date:
10-Jul-98     Release date:   08-Jun-99    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q02293  (FNTB_RAT) -  Protein farnesyltransferase subunit beta from Rattus norvegicus
Seq:
Struc: 		437 a.a.
400 a.a.
Protein chain
Pfam   ArchSchema ?
Q04631  (FNTA_RAT) -  Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha from Rattus norvegicus
Seq:
Struc: 		377 a.a.
316 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains B, A: E.C.2.5.1.58  - protein farnesyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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]
Bound ligand (Het Group name = PO4)
matches with 55.56% similarity 		+ diphosphate
      Cofactor: Mg(2+); Zn(2+)
   Enzyme class 2: Chain A: E.C.2.5.1.59  - protein geranylgeranyltransferase type I.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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]
Bound ligand (Het Group name = PO4)
matches with 55.56% similarity 		+ 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    
 
 
DOI no: 10.1021/bi980531o Biochemistry 37:7907-7912 (1998)
PubMed id: 9609683  
 
 
Protein farnesyltransferase: structure and implications for substrate binding.
P.Dunten, U.Kammlott, R.Crowther, D.Weber, R.Palermo, J.Birktoft.
 
  ABSTRACT  
 
The rat protein farnesyltransferase crystal structure has been solved by multiple isomorphous replacement methods at a resolution of 2.75 A. The three-dimensional structure, together with recent data on the effects of several mutations, led us to propose a model for substrate binding which differs from the model presented by Park et al. based on their independent structure determination [Park, H. -W., Boduluri, S. R., Moomaw, J. F., Casey, P. J., and Beese, L. S. (1997) Science 275, 1800-1804]. Both farnesyl diphosphate and peptide substrates can be accommodated in the hydrophobic active-site barrel, with the sole charged residue inside the barrel, Arg202 of the beta-subunit, forming a salt bridge with the negatively charged carboxy terminus of peptide substrates. Our proposals are based in part on the observation of electron density in the active site which can be modeled as bound farnesyl diphosphate carried through the enzyme purification. In addition, our model explains in structural terms the results of mutational studies which have identified several residues critical for substrate specificity and catalysis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19301336 S.F.Sousa, P.A.Fernandes, and M.J.Ramos (2009).
The search for the mechanism of the reaction catalyzed by farnesyltransferase.
  Chemistry, 15, 4243-4247.  
18985644 T.Subramanian, S.Liu, J.M.Troutman, D.A.Andres, and H.P.Spielmann (2008).
Protein farnesyltransferase-catalyzed isoprenoid transfer to peptide depends on lipid size and shape, not hydrophobicity.
  Chembiochem, 9, 2872-2882.  
17918965 G.Cui, and K.M.Merz (2007).
Computational studies of the farnesyltransferase ternary complex part II: the conformational activation of farnesyldiphosphate.
  Biochemistry, 46, 12375-12381.  
17979291 G.R.Labadie, R.Viswanathan, and C.D.Poulter (2007).
Farnesyl diphosphate analogues with omega-bioorthogonal azide and alkyne functional groups for protein farnesyl transferase-catalyzed ligation reactions.
  J Org Chem, 72, 9291-9297.  
17376731 J.Penner-Hahn (2007).
Zinc-promoted alkyl transfer: a new role for zinc.
  Curr Opin Chem Biol, 11, 166-171.  
17068802 S.F.Sousa, P.A.Fernandes, and M.J.Ramos (2007).
Theoretical studies on farnesyltransferase: the distances paradox explained.
  Proteins, 66, 205-218.  
16342942 G.Cui, B.Wang, and K.M.Merz (2005).
Computational studies of the farnesyltransferase ternary complex part I: substrate binding.
  Biochemistry, 44, 16513-16523.  
15661734 R.T.Eastman, J.White, O.Hucke, K.Bauer, K.Yokoyama, L.Nallan, D.Chakrabarti, C.L.Verlinde, M.H.Gelb, P.K.Rathod, and W.C.Van Voorhis (2005).
Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum.
  J Biol Chem, 280, 13554-13559.  
15501930 S.F.Sousa, P.A.Fernandes, and M.J.Ramos (2005).
Farnesyltransferase--new insights into the zinc-coordination sphere paradigm: evidence for a carboxylate-shift mechanism.
  Biophys J, 88, 483-494.  
15611883 S.F.Sousa, P.A.Fernandes, and M.J.Ramos (2005).
Unraveling the mechanism of the farnesyltransferase enzyme.
  J Biol Inorg Chem, 10, 3.  
16607571 W.C.Guida, A.D.Hamilton, J.W.Crotty, and S.M.Sebti (2005).
Protein farnesyltransferase: flexible docking studies on inhibitors using computational modeling.
  J Comput Aided Mol Des, 19, 871-885.  
14532266 J.S.Pickett, K.E.Bowers, and C.A.Fierke (2003).
Mutagenesis studies of protein farnesyltransferase implicate aspartate beta 352 as a magnesium ligand.
  J Biol Chem, 278, 51243-51250.  
14609943 J.S.Taylor, T.S.Reid, K.L.Terry, P.J.Casey, and L.S.Beese (2003).
Structure of mammalian protein geranylgeranyltransferase type-I.
  EMBO J, 22, 5963-5974.
PDB codes: 1n4p 1n4q 1n4r 1n4s
12510823 K.N.Cho, and K.I.Lee (2002).
Chemistry and biology of Ras farnesyltransferase.
  Arch Pharm Res, 25, 759-769.  
11170422 K.E.Hightower, P.J.Casey, and C.A.Fierke (2001).
Farnesylation of nonpeptidic thiol compounds by protein farnesyltransferase.
  Biochemistry, 40, 1002-1010.  
11170866 G.C.Prendergast, and A.Oliff (2000).
Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects.
  Semin Cancer Biol, 10, 443-452.  
10745007 H.Zhang, M.C.Seabra, and J.Deisenhofer (2000).
Crystal structure of Rab geranylgeranyltransferase at 2.0 A resolution.
  Structure, 8, 241-251.
PDB code: 1dce
10673434 S.B.Long, P.J.Casey, and L.S.Beese (2000).
The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures.
  Structure, 8, 209-222.
PDB codes: 1d8d 1d8e
  11106157 Y.P.Pang, K.Xu, J.E.Yazal, and F.G.Prendergas (2000).
Successful molecular dynamics simulation of the zinc-bound farnesyltransferase using the cationic dummy atom approach.
  Protein Sci, 9, 1857-1865.
PDB code: 1qe2
10382537 A.Oliff (1999).
Farnesyltransferase inhibitors: targeting the molecular basis of cancer.
  Biochim Biophys Acta, 1423, C19-C30.  
10491170 K.Alexandrov, I.Simon, V.Yurchenko, A.Iakovenko, E.Rostkova, A.J.Scheidig, and R.S.Goody (1999).
Characterization of the ternary complex between Rab7, REP-1 and Rab geranylgeranyl transferase.
  Eur J Biochem, 265, 160-170.  
10480914 K.Del Villar, J.Urano, L.Guo, and F.Tamanoi (1999).
A mutant form of human protein farnesyltransferase exhibits increased resistance to farnesyltransferase inhibitors.
  J Biol Chem, 274, 27010-27017.  
10226042 K.E.Hightower, and C.A.Fierke (1999).
Zinc-catalyzed sulfur alkyation:insights from protein farnesyltransferase.
  Curr Opin Chem Biol, 3, 176-181.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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