PDBsum entry 1pii

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Bifunctional(isomerase and synthase) PDB id
Protein chain
452 a.a. *
PO4 ×2
Waters ×628
* Residue conservation analysis
PDB id:
Name: Bifunctional(isomerase and synthase)
Title: Three-dimensional structure of the bifunctional enzyme phosphoribosylanthranilate isomerase: indoleglycerolphosphate synthase from escherichia coli refined at 2.0 angstroms resolution
Structure: N-(5'phosphoribosyl)anthranilate isomerase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562
2.00Å     R-factor:   0.173    
Authors: M.Wilmanns,J.P.Priestle,J.N.Jansonius
Key ref: M.Wilmanns et al. (1992). Three-dimensional structure of the bifunctional enzyme phosphoribosylanthranilate isomerase: indoleglycerolphosphate synthase from Escherichia coli refined at 2.0 A resolution. J Mol Biol, 223, 477-507. PubMed id: 1738159
21-Jun-91     Release date:   31-Jan-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00909  (TRPC_ECOLI) -  Tryptophan biosynthesis protein TrpCF
453 a.a.
452 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Indole-3-glycerol-phosphate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Tryptophan Biosynthesis
      Reaction: 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate = 1-C- (3-indolyl)-glycerol 3-phosphate + CO2 + H2O
1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate
= 1-C- (3-indolyl)-glycerol 3-phosphate
+ CO(2)
+ H(2)O
   Enzyme class 2: E.C.  - Phosphoribosylanthranilate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: N-(5-phospho-beta-D-ribosyl)anthranilate = 1-(2-carboxyphenylamino)-1- deoxy-D-ribulose 5-phosphate
= 1-(2-carboxyphenylamino)-1- deoxy-D-ribulose 5-phosphate
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 
  GO annot!
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     6 terms  


J Mol Biol 223:477-507 (1992)
PubMed id: 1738159  
Three-dimensional structure of the bifunctional enzyme phosphoribosylanthranilate isomerase: indoleglycerolphosphate synthase from Escherichia coli refined at 2.0 A resolution.
M.Wilmanns, J.P.Priestle, T.Niermann, J.N.Jansonius.
The three-dimensional structure of the monomeric bifunctional enzyme N-(5'-phosphoribosyl)anthranilate isomerase:indole-3-glycerol-phosphate synthase from Escherichia coli has been refined at 2.0 A resolution, using oscillation film data obtained from synchrotron radiation. The model includes the complete protein (452 residues), two phosphate ions and 628 water molecules. The final R-factor is 17.3% for all observed data between 15 and 2 A resolution. The root-mean-square deviations from ideal bond lengths and bond angles are 0.010 A and 3.2 degrees, respectively. The structure of N-(5'-phosphoribosyl)anthranilate isomerase: indole-3-glycerol-phosphate synthase from E. coli comprises two beta/alpha-barrel domains that superimpose with a root-mean-square deviation of 2.03 A for 138 C alpha-pairs. The C-terminal domain (residues 256 to 452) catalyses the PRAI reaction and the N-terminal domain (residues 1 to 255) catalyses the IGPS reaction, two sequential steps in tryptophan biosynthesis. The enzyme has the overall shape of a dumb-bell, resulting in a surface area that is considerably larger than normally observed for monomeric proteins of this size. The active sites of the PRAI and the IGPS domains, both located at the C-terminal side of the central beta-barrel, contain equivalent binding sites for the phosphate moieties of the substrates N-(5'-phosphoribosyl) anthranilate and 1-(o-carboxyphenylamino)-1-deoxyribulose-5-phosphate. These two phosphate binding sites are identical with respect to their positions within the tertiary structure of the beta/alpha-barrel, the conformation of the residues involved in phosphate binding and the hydrogen-bonding network between the phosphate ions and the protein. The active site cavities of both domains contain similar hydrophobic pockets that presumably bind the anthranilic acid moieties of the substrates. These similarities of the tertiary structures and the active sites of the two domains provide evidence that N-(5'-phosphoribosyl)anthranilate isomerase:indole-3-glycerol-phosphate synthase from E. coli results from a gene duplication event of a monomeric beta/alpha-barrel ancestor.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21058300 S.Akanuma, and A.Yamagishi (2011).
Roles for the two N-terminal (β/α) modules in the folding of a (β/α)₈-barrel protein as studied by fragmentation analysis.
  Proteins, 79, 221-231.  
21354426 S.Setiyaputra, J.P.Mackay, and W.M.Patrick (2011).
The structure of a truncated phosphoribosylanthranilate isomerase suggests a unified model for evolution of the (βα)8 barrel fold.
  J Mol Biol, 408, 291-303.
PDB code: 2kzh
20596542 A.Bhardwaj, S.Leelavathi, S.Mazumdar-Leighton, A.Ghosh, S.Ramakumar, and V.S.Reddy (2010).
The critical role of N- and C-terminal contact in protein stability and folding of a family 10 xylanase under extreme conditions.
  PLoS One, 5, e11347.  
20205445 R.G.Coleman, and K.A.Sharp (2010).
Protein pockets: inventory, shape, and comparison.
  J Chem Inf Model, 50, 589-603.  
19787060 X.Yang, S.V.Kathuria, R.Vadrevu, and C.R.Matthews (2009).
Betaalpha-hairpin clamps brace betaalphabeta modules and can make substantive contributions to the stability of TIM barrel proteins.
  PLoS One, 4, e7179.  
18272177 W.M.Patrick, and I.Matsumura (2008).
A study in molecular contingency: glutamine phosphoribosylpyrophosphate amidotransferase is a promiscuous and evolvable phosphoribosylanthranilate isomerase.
  J Mol Biol, 377, 323-336.  
15614829 S.Akanuma, H.Miyagawa, K.Kitamura, and A.Yamagishi (2005).
A detailed unfolding pathway of a (beta/alpha)8-barrel protein as studied by molecular dynamics simulations.
  Proteins, 58, 538-546.  
16008567 W.M.Patrick, and J.M.Blackburn (2005).
In vitro selection and characterization of a stable subdomain of phosphoribosylanthranilate isomerase.
  FEBS J, 272, 3684-3697.  
14760745 A.Linden, and M.Wilmanns (2004).
Adaptation of class-13 alpha-amylases to diverse living conditions.
  Chembiochem, 5, 231-239.  
11856350 A.Ivens, O.Mayans, H.Szadkowski, C.Jürgens, M.Wilmanns, and K.Kirschner (2002).
Stabilization of a (betaalpha)8-barrel protein by an engineered disulfide bridge.
  Eur J Biochem, 269, 1145-1153.
PDB code: 1jcm
11959448 M.P.Challen, C.Zhang, and T.J.Elliott (2002).
Agaricus bisporus and Coprinus bilanatus TRP2 genes are tri-functional with conserved intron and domain organisations.
  FEMS Microbiol Lett, 208, 269-274.  
11967367 P.Aloy, B.Oliva, E.Querol, F.X.Aviles, and R.B.Russell (2002).
Structural similarity to link sequence space: new potential superfamilies and implications for structural genomics.
  Protein Sci, 11, 1101-1116.  
11298741 A.Ivens, O.Mayans, H.Szadkowski, M.Wilmanns, and K.Kirschner (2001).
Purification, characterization and crystallization of thermostable anthranilate phosphoribosyltransferase from Sulfolobus solfataricus.
  Eur J Biochem, 268, 2246-2252.  
11395407 J.A.Gerlt, and P.C.Babbitt (2001).
Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies.
  Annu Rev Biochem, 70, 209-246.  
11106614 A.J.Orry, and B.A.Wallace (2000).
Modeling and docking the endothelin G-protein-coupled receptor.
  Biophys J, 79, 3083-3094.  
  11178260 J.A.Gerlt, and P.C.Babbitt (2000).
Can sequence determine function?
  Genome Biol, 1, REVIEWS0005.  
10745009 R.Thoma, M.Hennig, R.Sterner, and K.Kirschner (2000).
Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima.
  Structure, 8, 265-276.
PDB code: 1dl3
10545331 W.Grabarse, M.Vaupel, J.A.Vorholt, S.Shima, R.K.Thauer, A.Wittershagen, G.Bourenkov, H.D.Bartunik, and U.Ermler (1999).
The crystal structure of methenyltetrahydromethanopterin cyclohydrolase from the hyperthermophilic archaeon Methanopyrus kandleri.
  Structure, 7, 1257-1268.
PDB code: 1qlm
  9605328 B.Darimont, C.Stehlin, H.Szadkowski, and K.Kirschner (1998).
Mutational analysis of the active site of indoleglycerol phosphate synthase from Escherichia coli.
  Protein Sci, 7, 1221-1232.  
9016724 J.C.Eads, D.Ozturk, T.B.Wexler, C.Grubmeyer, and J.C.Sacchettini (1997).
A new function for a common fold: the crystal structure of quinolinic acid phosphoribosyltransferase.
  Structure, 5, 47-58.
PDB code: 1qap
9099709 T.Schwarz, K.Uthoff, C.Klinger, H.E.Meyer, P.Bartholmes, and M.Kaufmann (1997).
Multifunctional tryptophan-synthesizing enzyme. The molecular weight of the Euglena gracilis protein is unexpectedly low.
  J Biol Chem, 272, 10616-10623.  
18629858 C.Khosla, R.Caren, C.M.Kao, R.McDaniel, and S.W.Wang (1996).
Evolutionally guided enzyme design.
  Biotechnol Bioeng, 52, 122-128.  
  8897600 R.Sterner, G.R.Kleemann, H.Szadkowski, A.Lustig, M.Hennig, and K.Kirschner (1996).
Phosphoribosyl anthranilate isomerase from Thermotoga maritima is an extremely stable and active homodimer.
  Protein Sci, 5, 2000-2008.  
  8762144 S.Janecek (1996).
Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?
  Protein Sci, 5, 1136-1143.  
8747456 M.Hennig, B.Darimont, R.Sterner, K.Kirschner, and J.N.Jansonius (1995).
2.0 A structure of indole-3-glycerol phosphate synthase from the hyperthermophile Sulfolobus solfataricus: possible determinants of protein stability.
  Structure, 3, 1295-1306.
PDB code: 1igs
  7757015 P.Bork, J.Gellerich, H.Groth, R.Hooft, and F.Martin (1995).
Divergent evolution of a beta/alpha-barrel subclass: detection of numerous phosphate-binding sites by motif search.
  Protein Sci, 4, 268-274.  
  7556082 R.Sterner, A.Dahm, B.Darimont, A.Ivens, W.Liebl, and K.Kirschner (1995).
(Beta alpha)8-barrel proteins of tryptophan biosynthesis in the hyperthermophile Thermotoga maritima.
  EMBO J, 14, 4395-4402.  
8592705 T.Sandalova, and Y.Lindqvist (1995).
Three-dimensional model of the alpha-subunit of bacterial luciferase.
  Proteins, 23, 241-255.  
8710829 Y.Matsuo, and K.Nishikawa (1995).
Assessment of a protein fold recognition method that takes into account four physicochemical properties: side-chain packing, solvation, hydrogen-bonding, and local conformation.
  Proteins, 23, 370-375.  
8001582 T.Crombie, J.P.Boyle, J.R.Coggins, and A.J.Brown (1994).
The folding of the bifunctional TRP3 protein in yeast is influenced by a translational pause which lies in a region of structural divergence with Escherichia coli indoleglycerol-phosphate synthase.
  Eur J Biochem, 226, 657-664.  
  7849601 W.R.Taylor, T.P.Flores, and C.A.Orengo (1994).
Multiple protein structure alignment.
  Protein Sci, 3, 1858-1870.  
7922041 Y.Harpaz, M.Gerstein, and C.Chothia (1994).
Volume changes on protein folding.
  Structure, 2, 641-649.  
  8401235 C.Colovos, and T.O.Yeates (1993).
Verification of protein structures: patterns of nonbonded atomic interactions.
  Protein Sci, 2, 1511-1519.  
8234342 H.A.Schreuder, S.Knight, P.M.Curmi, I.Andersson, D.Cascio, C.I.Brändén, and D.Eisenberg (1993).
Formation of the active site of ribulose-1,5-bisphosphate carboxylase/oxygenase by a disorder-order transition from the unactivated to the activated form.
  Proc Natl Acad Sci U S A, 90, 9968-9972.  
  7508076 M.Riley (1993).
Functions of the gene products of Escherichia coli.
  Microbiol Rev, 57, 862-952.  
8433995 M.Wilmanns, and D.Eisenberg (1993).
Three-dimensional profiles from residue-pair preferences: identification of sequences with beta/alpha-barrel fold.
  Proc Natl Acad Sci U S A, 90, 1379-1383.  
8141995 S.Janecek, and S.Baláz (1993).
Evolution of parallel beta/alpha-barrel enzyme family lightened by structural data on starch-processing enzymes.
  J Protein Chem, 12, 509-514.  
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.