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PDBsum entry 1f75

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1f75
Jmol
Contents
Protein chains
217 a.a. *
Ligands
SO4 ×2
Waters ×38
* Residue conservation analysis
PDB id:
1f75
Name: Transferase
Title: Crystal structure of undecaprenyl diphosphate synthase from micrococcus luteus b-p 26
Structure: Undecaprenyl pyrophosphate synthetase. Chain: a, b. Engineered: yes. Mutation: yes
Source: Micrococcus luteus. Organism_taxid: 1270. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.20Å     R-factor:   0.190     R-free:   0.246
Authors: M.Fujihashi,Y.-W.Zhang,Y.Higuchi,X.-Y.Li,T.Koyama,K.Miki
Key ref:
M.Fujihashi et al. (2001). Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase. Proc Natl Acad Sci U S A, 98, 4337-4342. PubMed id: 11287651 DOI: 10.1073/pnas.071514398
Date:
26-Jun-00     Release date:   28-Mar-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O82827  (UPPS_MICLU) -  Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl-diphosphate specific)
Seq:
Struc:
249 a.a.
217 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.5.1.31  - Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl-
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Polyprenol biosynthesis
      Reaction: (2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + di-trans,octa-cis-undecaprenyl diphosphate
(2E,6E)-farnesyl diphosphate
+ 8 × isopentenyl diphosphate
= 8 × diphosphate
+ di-trans,octa-cis-undecaprenyl diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     transferase activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.071514398 Proc Natl Acad Sci U S A 98:4337-4342 (2001)
PubMed id: 11287651  
 
 
Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase.
M.Fujihashi, Y.W.Zhang, Y.Higuchi, X.Y.Li, T.Koyama, K.Miki.
 
  ABSTRACT  
 
Undecaprenyl diphosphate synthase (UPS) catalyzes the cis-prenyl chain elongation onto trans, trans-farnesyl diphosphate (FPP) to produce undecaprenyl diphosphate (UPP), which is indispensable for the biosynthesis of bacterial cell walls. We report here the crystal structure of UPS as the only three-dimensional structure among cis-prenyl chain elongating enzymes. The structure is classified into a protein fold family and is completely different from the so-called "isoprenoid synthase fold" that is believed to be a common structure for the enzymes relating to isoprenoid biosynthesis. Conserved amino acid residues among cis-prenyl chain elongating enzymes are located around a large hydrophobic cleft in the UPS structure. A structural P-loop motif, which frequently appears in the various kinds of phosphate binding site, is found at the entrance of this cleft. The catalytic site is determined on the basis of these structural features, from which a possible reaction mechanism is proposed.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. A schematic drawing of the biosynthesis related to prenyl chains. UPS catalyzes 8× cis-prenyl chain elongation step by step. Both cis- and trans-prenyl chains are constructed from the same substrates by the cis or trans types of prenyltransferase, in which the only difference is the cis- and trans-isomerism of the prenyl chain product.
Figure 4.
Fig. 4. Hypothetical FPP and IPP binding model with UPS. (A) Stereo view of the molecular surface of UPS (gray envelope) and the bindings of FPP and IPP (C, O, and P atoms in green, pink, and orange, respectively). The estimated position of the magnesium ion is shown by the brown sphere. This figure was prepared by using MOLSCRIPT (33), GRASP (35), and RASTER3D (34). (B) Schematic presentation of a binding model. The UPS structure is shown in green.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20737255 G.Reuther, R.Harris, M.Girvin, and T.S.Leyh (2011).
Backbone (1)H, (13)C, (15)N NMR assignments of the unliganded and substrate ternary complex forms of mevalonate diphosphate decarboxylase from Streptococcus pneumoniae.
  Biomol NMR Assign, 5, 11-14.  
21295283 S.Züchner, J.Dallman, R.Wen, G.Beecham, A.Naj, A.Farooq, M.A.Kohli, P.L.Whitehead, W.Hulme, I.Konidari, Y.J.Edwards, G.Cai, I.Peter, D.Seo, J.D.Buxbaum, J.L.Haines, S.Blanton, J.Young, E.Alfonso, J.M.Vance, B.L.Lam, and M.A.Peričak-Vance (2011).
Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa.
  Am J Hum Genet, 88, 201-206.  
20685834 J.S.Rush, S.Matveev, Z.Guan, C.R.Raetz, and C.J.Waechter (2010).
Expression of functional bacterial undecaprenyl pyrophosphate synthase in the yeast rer2{Delta} mutant and CHO cells.
  Glycobiology, 20, 1585-1593.  
20308470 K.A.Grabińska, J.Cui, A.Chatterjee, Z.Guan, C.R.Raetz, P.W.Robbins, and J.Samuelson (2010).
Molecular characterization of the cis-prenyltransferase of Giardia lamblia.
  Glycobiology, 20, 824-832.  
20476728 L.V.Lee, B.Granda, K.Dean, J.Tao, E.Liu, R.Zhang, S.Peukert, S.Wattanasin, X.Xie, N.S.Ryder, R.Tommasi, and G.Deng (2010).
Biophysical investigation of the mode of inhibition of tetramic acids, the allosteric inhibitors of undecaprenyl pyrophosphate synthase.
  Biochemistry, 49, 5366-5376.  
19323569 C.D.Poulter, and C.D.Poulter (2009).
Bioorganic chemistry. A natural reunion of the physical and life sciences.
  J Org Chem, 74, 2631-2645.  
18081839 A.Bouhss, A.E.Trunkfield, T.D.Bugg, and D.Mengin-Lecreulx (2008).
The biosynthesis of peptidoglycan lipid-linked intermediates.
  FEMS Microbiol Rev, 32, 208-233.  
19053772 D.Mukkamala, J.H.No, L.M.Cass, T.K.Chang, and E.Oldfield (2008).
Bisphosphonate inhibition of a Plasmodium farnesyl diphosphate synthase and a general method for predicting cell-based activity from enzyme data.
  J Med Chem, 51, 7827-7833.  
18323637 K.Fujikura, Y.Maki, N.Ohya, M.Satoh, and T.Koyama (2008).
Kinetic studies of Micrococcus luteus B-P 26 undecaprenyl diphosphate synthase reaction using 3-desmethyl allylic substrate analogs.
  Biosci Biotechnol Biochem, 72, 851-855.  
18597781 W.Wang, C.Dong, M.McNeil, D.Kaur, S.Mahapatra, D.C.Crick, and J.H.Naismith (2008).
The structural basis of chain length control in Rv1086.
  J Mol Biol, 381, 129-140.
PDB codes: 2vfw 2vg0 2vg1 2vg2 2vg3 2vg4
17345630 J.Poznański, and A.Szkopinska (2007).
Precise bacterial polyprenol length control fails in Saccharomyces cerevisiae.
  Biopolymers, 86, 155-164.  
17147392 H.V.Thulasiram, and C.D.Poulter (2006).
Farnesyl diphosphate synthase: the art of compromise between substrate selectivity and stereoselectivity.
  J Am Chem Soc, 128, 15819-15823.  
16420487 Y.Kharel, S.Takahashi, S.Yamashita, and T.Koyama (2006).
Manipulation of prenyl chain length determination mechanism of cis-prenyltransferases.
  FEBS J, 273, 647-657.  
16289312 F.Bouvier, A.Rahier, and B.Camara (2005).
Biogenesis, molecular regulation and function of plant isoprenoids.
  Prog Lipid Res, 44, 357-429.  
15952894 J.Stubbe, J.Tian, A.He, A.J.Sinskey, A.G.Lawrence, and P.Liu (2005).
Nontemplate-dependent polymerization processes: polyhydroxyalkanoate synthases as a paradigm.
  Annu Rev Biochem, 74, 433-480.  
15044730 S.Y.Chang, T.P.Ko, A.P.Chen, A.H.Wang, and P.H.Liang (2004).
Substrate binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies.
  Protein Sci, 13, 971-978.
PDB code: 1v7u
14511375 C.J.Mau, S.Garneau, A.A.Scholte, J.E.Van Fleet, J.C.Vederas, and K.Cornish (2003).
Protein farnesyltransferase inhibitors interfere with farnesyl diphosphate binding by rubber transferase.
  Eur J Biochem, 270, 3939-3945.  
14622254 K.Asawatreratanakul, Y.W.Zhang, D.Wititsuwannakul, R.Wititsuwannakul, S.Takahashi, A.Rattanapittayaporn, and T.Koyama (2003).
Molecular cloning, expression and characterization of cDNA encoding cis-prenyltransferases from Hevea brasiliensis. A key factor participating in natural rubber biosynthesis.
  Eur J Biochem, 270, 4671-4680.  
14661956 S.Y.Chang, Y.K.Chen, A.H.Wang, and P.H.Liang (2003).
Identification of the active conformation and the importance of length of the flexible loop 72-83 in regulating the conformational change of undecaprenyl pyrophosphate synthase.
  Biochemistry, 42, 14452-14459.  
11901475 D.W.Green (2002).
The bacterial cell wall as a source of antibacterial targets.
  Expert Opin Ther Targets, 6, 1.  
12702274 K.Grabińska, and G.Palamarczyk (2002).
Dolichol biosynthesis in the yeast Saccharomyces cerevisiae: an insight into the regulatory role of farnesyl diphosphate synthase.
  FEMS Yeast Res, 2, 259-265.  
12135472 P.H.Liang, T.P.Ko, and A.H.Wang (2002).
Structure, mechanism and function of prenyltransferases.
  Eur J Biochem, 269, 3339-3354.  
11698643 M.J.Rynkiewicz, D.E.Cane, and D.W.Christianson (2001).
Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade.
  Proc Natl Acad Sci U S A, 98, 13543-13548.
PDB codes: 1jfa 1jfg
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.