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PDBsum entry 1n4q
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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1n4q

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
(+ 0 more) 314 a.a. *
(+ 0 more) 346 a.a. *
Ligands
LYS-CYS-VAL-ILE-
LEU ×6
MGM ×6
GER
Metals
_CL ×7
_ZN ×6
Waters ×1117
* Residue conservation analysis
PDB id:
1n4q
Name: Transferase
Title: Protein geranylgeranyltransferase type-i complexed with a ggpp analog and a kkksktkcvil peptide
Structure: Protein farnesyltransferase/geranylgeranyltransferase type- 1 subunit alpha. Chain: a, c, e, g, i, k. Synonym: caax farnesyltransferase subunit alpha,ftase-alpha,ras proteins prenyltransferase subunit alpha,type i protein geranyl- geranyltransferase subunit alpha,ggtase-i-alpha. Engineered: yes. Geranylgeranyl transferase type-1 subunit beta. Chain: b, d, f, h, j, l.
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: fnta. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: pggt1b. Synthetic: yes. Homo sapiens.
Biol. unit: 80mer (from PQS)
Resolution:
2.40Å     R-factor:   0.214     R-free:   0.234
Authors: J.S.Taylor,T.S.Reid,P.J.Casey,L.S.Beese
Key ref: J.S.Taylor et al. (2003). Structure of mammalian protein geranylgeranyltransferase type-I. Embo J, 22, 5963-5974. PubMed id: 14609943
Date:
01-Nov-02     Release date:   18-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q04631  (FNTA_RAT) -  Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha from Rattus norvegicus
Seq:
Struc: 		377 a.a.
314 a.a.
Protein chains
Pfam   ArchSchema ?
P53610  (PGTB1_RAT) -  Geranylgeranyl transferase type-1 subunit beta from Rattus norvegicus
Seq:
Struc: 		377 a.a.
346 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, C, E, G, I, K: 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 = GER)
matches with 51.72% similarity 		+ (2E,6E)-farnesyl diphosphate
 = S-(2E,6E)- farnesyl-L-cysteinyl-[protein]
 + diphosphate
      Cofactor: Mg(2+); Zn(2+)
   Enzyme class 2: Chains A, B, C, D, E, F, G, H, I, J, K, L: 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 = GER)
matches with 68.97% 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    
 
 
Embo J 22:5963-5974 (2003)
PubMed id: 14609943  
 
 
Structure of mammalian protein geranylgeranyltransferase type-I.
J.S.Taylor, T.S.Reid, K.L.Terry, P.J.Casey, L.S.Beese.
 
  ABSTRACT  
 
Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first structural information for mammalian GGTase-I, including a series of substrate and product complexes that delineate the path of the chemical reaction. These structures reveal that all protein prenyltransferases share a common reaction mechanism and identify specific residues that play a dominant role in determining prenyl group specificity. This hypothesis was confirmed by converting farnesyltransferase (15-C prenyl substrate) into GGTase-I (20-C prenyl substrate) with a single point mutation. GGTase-I discriminates against farnesyl diphosphate (FPP) at the product turnover step through the inability of a 15-C FPP to displace the 20-C prenyl-peptide product. Understanding these key features of specificity is expected to contribute to optimization of anti-cancer and anti-parasite drugs.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20490881 J.A.Tamames, and M.J.Ramos (2011).
Metals in proteins: cluster analysis studies.
  J Mol Model, 17, 429-442.  
20531405 C.M.Owens, C.Mawhinney, J.M.Grenier, R.Altmeyer, M.S.Lee, A.A.Borisy, J.Lehár, and L.M.Johansen (2010).
Chemical combinations elucidate pathway interactions and regulation relevant to Hepatitis C replication.
  Mol Syst Biol, 6, 375.  
20565889 M.Andrews, D.H.Huizinga, and D.N.Crowell (2010).
The CaaX specificities of Arabidopsis protein prenyltransferases explain era1 and ggb phenotypes.
  BMC Plant Biol, 10, 118.  
19954434 M.L.Hovlid, R.L.Edelstein, O.Henry, J.Ochocki, A.DeGraw, S.Lenevich, T.Talbot, V.G.Young, A.W.Hruza, F.Lopez-Gallego, N.P.Labello, C.L.Strickland, C.Schmidt-Dannert, and M.D.Distefano (2010).
Synthesis, properties, and applications of diazotrifluropropanoyl-containing photoactive analogs of farnesyl diphosphate containing modified linkages for enhanced stability.
  Chem Biol Drug Des, 75, 51-67.
PDB code: 3ksl
20446922 S.S.Virtanen, J.Sandholm, G.Yegutkin, H.Kalervo Väänänen, and P.L.Härkönen (2010).
Inhibition of GGTase-I and FTase disrupts cytoskeletal organization of human PC-3 prostate cancer cells.
  Cell Biol Int, 34, 815-826.  
20432425 U.T.Nguyen, R.S.Goody, and K.Alexandrov (2010).
Understanding and exploiting protein prenyltransferases.
  Chembiochem, 11, 1194-1201.  
19784953 L.N.Chan, C.Hart, L.Guo, T.Nyberg, B.S.Davies, L.G.Fong, S.G.Young, B.J.Agnew, and F.Tamanoi (2009).
A novel approach to tag and identify geranylgeranylated proteins.
  Electrophoresis, 30, 3598-3606.  
19246009 M.A.Hast, S.Fletcher, C.G.Cummings, E.E.Pusateri, M.A.Blaskovich, K.Rivas, M.H.Gelb, W.C.Van Voorhis, S.M.Sebti, A.D.Hamilton, and L.S.Beese (2009).
Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase.
  Chem Biol, 16, 181-192.
PDB codes: 3e30 3e32 3e33 3e34 3e37
19074143 R.A.Baron, R.Tavaré, A.C.Figueiredo, K.M.Blazewska, B.A.Kashemirov, C.E.McKenna, F.H.Ebetino, A.Taylor, M.J.Rogers, F.P.Coxon, and M.C.Seabra (2009).
Phosphonocarboxylates inhibit the second geranylgeranyl addition by rab geranylgeranyl transferase.
  J Biol Chem, 284, 6861-6868.  
18648687 A.I.Anzellotti, and N.P.Farrell (2008).
Zinc metalloproteins as medicinal targets.
  Chem Soc Rev, 37, 1629-1651.  
18176953 J.S.Weiss, H.S.Kruth, H.Kuivaniemi, G.Tromp, J.Karkera, S.Mahurkar, W.Lisch, W.J.Dupps, P.S.White, R.S.Winters, C.Kim, C.J.Rapuano, J.Sutphin, J.Reidy, F.R.Hu, d.a. .W.Lu, N.Ebenezer, and M.L.Nickerson (2008).
Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function.
  Am J Med Genet A, 146, 271-283.  
17996962 K.Yokoyama, J.R.Gillespie, W.C.Van Voorhis, F.S.Buckner, and M.H.Gelb (2008).
Protein geranylgeranyltransferase-I of Trypanosoma cruzi.
  Mol Biochem Parasitol, 157, 32-43.  
18713740 M.A.Hast, and L.S.Beese (2008).
Structure of Protein Geranylgeranyltransferase-I from the Human Pathogen Candida albicans Complexed with a Lipid Substrate.
  J Biol Chem, 283, 31933-31940.
PDB code: 3dra
18230616 M.Watanabe, H.D.Fiji, L.Guo, L.Chan, S.S.Kinderman, D.J.Slamon, O.Kwon, and F.Tamanoi (2008).
Inhibitors of protein geranylgeranyltransferase I and Rab geranylgeranyltransferase identified from a library of allenoate-derived compounds.
  J Biol Chem, 283, 9571-9579.  
18756270 Z.Guo, Y.W.Wu, D.Das, C.Delon, J.Cramer, S.Yu, S.Thuns, N.Lupilova, H.Waldmann, L.Brunsveld, R.S.Goody, K.Alexandrov, and W.Blankenfeldt (2008).
Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation.
  EMBO J, 27, 2444-2456.
PDB codes: 3dss 3dst 3dsu 3dsv 3dsw 3dsx
18499677 d.a. .Y.Oh, J.M.Yoon, M.J.Moon, J.I.Hwang, H.Choe, J.Y.Lee, J.I.Kim, S.Kim, H.Rhim, D.K.O'Dell, J.M.Walker, H.S.Na, M.G.Lee, H.B.Kwon, K.Kim, and J.Y.Seong (2008).
Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92.
  J Biol Chem, 283, 21054-21064.  
17652517 C.Coffinier, S.E.Hudon, E.A.Farber, S.Y.Chang, C.A.Hrycyna, S.G.Young, and L.G.Fong (2007).
HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells.
  Proc Natl Acad Sci U S A, 104, 13432-13437.  
17705859 R.Rasteiro, and J.B.Pereira-Leal (2007).
Multiple domain insertions and losses in the evolution of the Rab prenylation complex.
  BMC Evol Biol, 7, 140.  
16892354 F.Minutolo, S.Bertini, L.Betti, R.Danesi, G.Gervasi, G.Giannaccini, A.Martinelli, A.M.Papini, E.Peroni, G.Placanica, S.Rapposelli, T.Tuccinardi, and M.Macchia (2006).
Synthesis of stable analogues of geranylgeranyl diphosphate possessing a (Z,E,E)-geranylgeranyl side chain, docking analysis, and biological assays for prenyl protein transferase inhibition.
  ChemMedChem, 1, 218-224.  
16633570 H.Peng, D.Carrico, V.Thai, M.Blaskovich, C.Bucher, E.E.Pusateri, S.M.Sebti, and A.D.Hamilton (2006).
Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I.
  Org Biomol Chem, 4, 1768-1784.  
16446806 J.Ohkanda, C.L.Strickland, M.A.Blaskovich, D.Carrico, J.W.Lockman, A.Vogt, C.J.Bucher, J.Sun, Y.Qian, D.Knowles, E.E.Pusateri, S.M.Sebti, and A.D.Hamilton (2006).
Structure-based design of imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase.
  Org Biomol Chem, 4, 482-492.  
16377641 J.Payandeh, M.Fujihashi, W.Gillon, and E.F.Pai (2006).
The crystal structure of (S)-3-O-geranylgeranylglyceryl phosphate synthase reveals an ancient fold for an ancient enzyme.
  J Biol Chem, 281, 6070-6078.
PDB codes: 2f6u 2f6x
16983387 M.H.Gelb, L.Brunsveld, C.A.Hrycyna, S.Michaelis, F.Tamanoi, W.C.Van Voorhis, and H.Waldmann (2006).
Therapeutic intervention based on protein prenylation and associated modifications.
  Nat Chem Biol, 2, 518-528.  
15659645 D.Michaelson, W.Ali, V.K.Chiu, M.Bergo, J.Silletti, L.Wright, S.G.Young, and M.Philips (2005).
Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases.
  Mol Biol Cell, 16, 1606-1616.  
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.  
15960807 S.Maurer-Stroh, and F.Eisenhaber (2005).
Refinement and prediction of protein prenylation motifs.
  Genome Biol, 6, R55.  
15131129 H.L.Hartman, K.E.Bowers, and C.A.Fierke (2004).
Lysine beta311 of protein geranylgeranyltransferase type I partially replaces magnesium.
  J Biol Chem, 279, 30546-30553.  
15128936 M.P.Running, M.Lavy, H.Sternberg, A.Galichet, W.Gruissem, S.Hake, N.Ori, and S.Yalovsky (2004).
Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases.
  Proc Natl Acad Sci U S A, 101, 7815-7820.  
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 code is shown on the right.

 

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