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

 

 

 

 

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Contents
Protein chains
492 a.a. *
Ligands
ONL ×2
PCP ×2
Metals
_MN ×5
Waters ×291
* Residue conservation analysis
PDB id:
1ecc
Name: Transferase
Title: Escherichia coli glutamine phosphoribosylpyrophosphate (prpp) amidotransferase complexed with mn-cprpp and 5-oxo-norleucine
Structure: Glutamine phosphoribosylpyrophosphate amidotransferase. Chain: a, b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: purf. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.40Å     R-factor:   0.176     R-free:   0.265
Authors: J.M.Krahn,J.L.Smith
Key ref:
J.M.Krahn et al. (1997). Coupled formation of an amidotransferase interdomain ammonia channel and a phosphoribosyltransferase active site. Biochemistry, 36, 11061-11068. PubMed id: 9333323 DOI: 10.1021/bi9714114
Date:
09-Jul-97     Release date:   15-Apr-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P0AG16  (PUR1_ECOLI) -  Amidophosphoribosyltransferase from Escherichia coli (strain K12)
Seq:
Struc: 		505 a.a.
492 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.4.2.14  - amidophosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 5-phospho-beta-D-ribosylamine + L-glutamate + diphosphate = 5-phospho- alpha-D-ribose 1-diphosphate + L-glutamine + H2O
5-phospho-beta-D-ribosylamine
 + L-glutamate
 +
diphosphate
Bound ligand (Het Group name = ONL)
matches with 81.82% similarity 		=
5-phospho- alpha-D-ribose 1-diphosphate
Bound ligand (Het Group name = PCP)
matches with 91.30% similarity 		+ L-glutamine
 + H2O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/bi9714114 Biochemistry 36:11061-11068 (1997)
PubMed id: 9333323  
 
 
Coupled formation of an amidotransferase interdomain ammonia channel and a phosphoribosyltransferase active site.
J.M.Krahn, J.H.Kim, M.R.Burns, R.J.Parry, H.Zalkin, J.L.Smith.
 
  ABSTRACT  
 
Activation of gluatmine phosphoribosylpyrophosphate (RPPP) amidotransferase (GPATase) by binding of a PRPP substrate analog results in the formation of a 20 A channel connecting the active site for glutamine hydrolysis in one domain with the PRPP site in a second domain. This solvent-inaccessible channel permits transfer of the NH3 intermediate between the two active sites. Tunneling of NH3 may be a common mechanism for glutamine amidotransferase-catalyzed nitrogen transfer and for coordination of catalysis at two distinct active sites in complex enzymes. The 2.4 A crystal structure of the active conformer of GPATase also provides the first description of an intact active site for the phosphoribosyltransferase (PRTase) family of nucleotide synthesis and salvage enzymes. Chemical assistance to catalysis is provided primarily by the substrate and secondarily by the enzyme in the proposed structure-based mechanism. Different catalytic and inhibitory modes of divalent cation binding to the PRTase active site are revealed in the active conformer of the enzyme and in a feedback-inhibited GMP complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21134639 J.M.Lipchock, and J.P.Loria (2010).
Nanometer propagation of millisecond motions in V-type allostery.
  Structure, 18, 1596-1607.  
20590527 K.Hölsch, and D.Weuster-Botz (2010).
Enantioselective reduction of prochiral ketones by engineered bifunctional fusion proteins.
  Biotechnol Appl Biochem, 56, 131-140.  
20187643 L.Lund, Y.Fan, Q.Shao, Y.Q.Gao, and F.M.Raushel (2010).
Carbamate transport in carbamoyl phosphate synthetase: a theoretical and experimental investigation.
  J Am Chem Soc, 132, 3870-3878.  
19819904 R.Takahashi, S.Nakamura, T.Nakazawa, K.Minoura, T.Yoshida, Y.Nishi, Y.Kobayashi, and T.Ohkubo (2010).
Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase.
  J Biochem, 147, 95.
PDB codes: 2e5b 2e5c 2e5d
19565337 J.Lipchock, and J.P.Loria (2009).
Millisecond dynamics in the allosteric enzyme imidazole glycerol phosphate synthase (IGPS) from Thermotoga maritima.
  J Biomol NMR, 45, 73-84.  
18948259 R.L.Switzer (2009).
Discoveries in bacterial nucleotide metabolism.
  J Biol Chem, 284, 6585-6594.  
19569682 Y.Fan, L.Lund, Q.Shao, Y.Q.Gao, and F.M.Raushel (2009).
A combined theoretical and experimental study of the ammonia tunnel in carbamoyl phosphate synthetase.
  J Am Chem Soc, 131, 10211-10219.  
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.  
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
17951049 S.Mouilleron, and B.Golinelli-Pimpaneau (2007).
Conformational changes in ammonia-channeling glutamine amidotransferases.
  Curr Opin Struct Biol, 17, 653-664.  
16756505 N.G.Richards, and M.S.Kilberg (2006).
Asparagine synthetase chemotherapy.
  Annu Rev Biochem, 75, 629-654.  
16339762 S.Mouilleron, M.A.Badet-Denisot, and B.Golinelli-Pimpaneau (2006).
Glutamine binding opens the ammonia channel and activates glucosamine-6P synthase.
  J Biol Chem, 281, 4404-4412.
PDB codes: 2bpj 2bpl 2j6h 4amv
15911615 J.Zhu, J.W.Burgner, E.Harms, B.R.Belitsky, and J.L.Smith (2005).
A new arrangement of (beta/alpha)8 barrels in the synthase subunit of PLP synthase.
  J Biol Chem, 280, 27914-27923.
PDB code: 1znn
15716449 P.Chander, K.M.Halbig, J.K.Miller, C.J.Fields, H.K.Bonner, G.K.Grabner, R.L.Switzer, and J.L.Smith (2005).
Structure of the nucleotide complex of PyrR, the pyr attenuation protein from Bacillus caldolyticus, suggests dual regulation by pyrimidine and purine nucleotides.
  J Bacteriol, 187, 1773-1782.
PDB codes: 1non 1xz8 1xzn
15805504 Y.Mitani, X.Meng, Y.Kamagata, and T.Tamura (2005).
Characterization of LtsA from Rhodococcus erythropolis, an enzyme with glutamine amidotransferase activity.
  J Bacteriol, 187, 2582-2591.  
15511226 F.A.Lunn, and S.L.Bearne (2004).
Alternative substrates for wild-type and L109A E. coli CTP synthases: kinetic evidence for a constricted ammonia tunnel.
  Eur J Biochem, 271, 4204-4212.  
15189875 J.D.Lawson, E.Pate, I.Rayment, and R.G.Yount (2004).
Molecular dynamics analysis of structural factors influencing back door pi release in myosin.
  Biophys J, 86, 3794-3803.  
15289603 L.Salomonsson, A.Lee, R.B.Gennis, and P.Brzezinski (2004).
A single-amino-acid lid renders a gas-tight compartment within a membrane-bound transporter.
  Proc Natl Acad Sci U S A, 101, 11617-11621.  
12837784 A.K.Bera, J.Zhu, H.Zalkin, and J.L.Smith (2003).
Functional dissection of the Bacillus subtilis pur operator site.
  J Bacteriol, 185, 4099-4109.
PDB code: 1p4a
12738780 A.Saeed-Kothe, and S.G.Powers-Lee (2003).
Gain of glutaminase function in mutants of the ammonia-specific frog carbamoyl phosphate synthetase.
  J Biol Chem, 278, 26722-26726.  
12764229 B.A.Manjasetty, J.Powlowski, and A.Vrielink (2003).
Crystal structure of a bifunctional aldolase-dehydrogenase: sequestering a reactive and volatile intermediate.
  Proc Natl Acad Sci U S A, 100, 6992-6997.
PDB code: 1nvm
12482852 G.K.Grabner, and R.L.Switzer (2003).
Kinetic studies of the uracil phosphoribosyltransferase reaction catalyzed by the Bacillus subtilis pyrimidine attenuation regulatory protein PyrR.
  J Biol Chem, 278, 6921-6927.  
12799468 R.Amaro, E.Tajkhorshid, and Z.Luthey-Schulten (2003).
Developing an energy landscape for the novel function of a (beta/alpha)8 barrel: ammonia conduction through HisF.
  Proc Natl Acad Sci U S A, 100, 7599-7604.  
12837783 S.C.Sinha, J.Krahn, B.S.Shin, D.R.Tomchick, H.Zalkin, and J.L.Smith (2003).
The purine repressor of Bacillus subtilis: a novel combination of domains adapted for transcription regulation.
  J Bacteriol, 185, 4087-4098.
PDB codes: 1o57 1p41
11839304 A.Douangamath, M.Walker, S.Beismann-Driemeyer, M.C.Vega-Fernandez, R.Sterner, and M.Wilmanns (2002).
Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex.
  Structure, 10, 185-193.
PDB codes: 1gpw 1k9v
12037295 A.Kadziola, J.Neuhard, and S.Larsen (2002).
Structure of product-bound Bacillus caldolyticus uracil phosphoribosyltransferase confirms ordered sequential substrate binding.
  Acta Crystallogr D Biol Crystallogr, 58, 936-945.
PDB code: 1i5e
12130656 J.B.Thoden, X.Huang, F.M.Raushel, and H.M.Holden (2002).
Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia.
  J Biol Chem, 277, 39722-39727.
PDB code: 1m6v
11948179 K.G.Bulock, G.P.Beardsley, and K.S.Anderson (2002).
The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase). A surprising lack of substrate channeling.
  J Biol Chem, 277, 22168-22174.  
11773618 M.A.Schumacher, C.J.Bashor, M.H.Song, K.Otsu, S.Zhu, R.J.Parry, B.Ullman, and R.G.Brennan (2002).
The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase.
  Proc Natl Acad Sci U S A, 99, 78-83.
PDB codes: 1jlr 1jls
11967268 R.H.van den Heuvel, D.Ferrari, R.T.Bossi, S.Ravasio, B.Curti, M.A.Vanoni, F.J.Florencio, and A.Mattevi (2002).
Structural studies on the synchronization of catalytic centers in glutamate synthase.
  J Biol Chem, 277, 24579-24583.
PDB codes: 1llw 1llz 1lm1
11790837 T.A.Eriksen, A.Kadziola, and S.Larsen (2002).
Binding of cations in Bacillus subtilis phosphoribosyldiphosphate synthetase and their role in catalysis.
  Protein Sci, 11, 271-279.
PDB code: 1ibs
11987159 A.Bergner, J.Günther, M.Hendlich, G.Klebe, and M.Verdonk (2001).
Use of Relibase for retrieving complex three-dimensional interaction patterns including crystallographic packing effects.
  Biopolymers, 61, 99.  
11691917 I.Nobeli, R.A.Laskowski, W.S.Valdar, and J.M.Thornton (2001).
On the molecular discrimination between adenine and guanine by proteins.
  Nucleic Acids Res, 29, 4294-4309.  
11208798 T.J.Klem, Y.Chen, and V.J.Davisson (2001).
Subunit interactions and glutamine utilization by Escherichia coli imidazole glycerol phosphate synthase.
  J Bacteriol, 183, 989-996.  
11395405 X.Huang, H.M.Holden, and F.M.Raushel (2001).
Channeling of substrates and intermediates in enzyme-catalyzed reactions.
  Annu Rev Biochem, 70, 149-180.  
10713115 A.K.Bera, J.L.Smith, and H.Zalkin (2000).
Dual role for the glutamine phosphoribosylpyrophosphate amidotransferase ammonia channel. Interdomain signaling and intermediate channeling.
  J Biol Chem, 275, 7975-7979.  
10850988 A.K.Bera, S.Chen, J.L.Smith, and H.Zalkin (2000).
Temperature-dependent function of the glutamine phosphoribosylpyrophosphate amidotransferase ammonia channel and coupling with glycinamide ribonucleotide synthetase in a hyperthermophile.
  J Bacteriol, 182, 3734-3739.  
11188694 C.Binda, R.T.Bossi, S.Wakatsuki, S.Arzt, A.Coda, B.Curti, M.A.Vanoni, and A.Mattevi (2000).
Cross-talk and ammonia channeling between active centers in the unexpected domain arrangement of glutamate synthase.
  Structure, 8, 1299-1308.
PDB code: 1ea0
10673422 D.Kohls, T.Sulea, E.O.Purisima, R.E.MacKenzie, and A.Vrielink (2000).
The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme.
  Structure, 8, 35-46.
PDB code: 1qd1
11030421 S.Reumann (2000).
The structural properties of plant peroxisomes and their metabolic significance.
  Biol Chem, 381, 639-648.  
11006546 T.J.Kappock, S.E.Ealick, and J.Stubbe (2000).
Modular evolution of the purine biosynthetic pathway.
  Curr Opin Chem Biol, 4, 567-572.  
10841757 W.Shi, N.R.Munagala, C.C.Wang, C.M.Li, P.C.Tyler, R.H.Furneaux, C.Grubmeyer, V.L.Schramm, and S.C.Almo (2000).
Crystal structures of Giardia lamblia guanine phosphoribosyltransferase at 1.75 A(,).
  Biochemistry, 39, 6781-6790.
PDB codes: 1dqn 1dqp
10727215 X.Huang, and F.M.Raushel (2000).
An engineered blockage within the ammonia tunnel of carbamoyl phosphate synthetase prevents the use of glutamine as a substrate but not ammonia.
  Biochemistry, 39, 3240-3247.  
10593947 A.K.Bera, S.Chen, J.L.Smith, and H.Zalkin (1999).
Interdomain signaling in glutamine phosphoribosylpyrophosphate amidotransferase.
  J Biol Chem, 274, 36498-36504.  
10393170 C.L.Phillips, B.Ullman, R.G.Brennan, and C.P.Hill (1999).
Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani.
  EMBO J, 18, 3533-3545.
PDB codes: 1qb7 1qb8 1qcc 1qcd
10508786 C.Li, T.J.Kappock, J.Stubbe, T.M.Weaver, and S.E.Ealick (1999).
X-ray crystal structure of aminoimidazole ribonucleotide synthetase (PurM), from the Escherichia coli purine biosynthetic pathway at 2.5 A resolution.
  Structure, 7, 1155-1166.
PDB code: 1cli
10079076 C.Lundegaard, and K.F.Jensen (1999).
Kinetic mechanism of uracil phosphoribosyltransferase from Escherichia coli and catalytic importance of the conserved proline in the PRPP binding site.
  Biochemistry, 38, 3327-3334.  
10212181 E.W.Miles, S.Rhee, and D.R.Davies (1999).
The molecular basis of substrate channeling.
  J Biol Chem, 274, 12193-12196.  
10387030 F.M.Raushel, J.B.Thoden, and H.M.Holden (1999).
The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia.
  Biochemistry, 38, 7891-7899.  
  10338013 G.K.Balendiran, J.A.Molina, Y.Xu, J.Torres-Martinez, R.Stevens, P.J.Focia, A.E.Eakin, J.C.Sacchettini, and S.P.Craig (1999).
Ternary complex structure of human HGPRTase, PRPP, Mg2+, and the inhibitor HPP reveals the involvement of the flexible loop in substrate binding.
  Protein Sci, 8, 1023-1031.
PDB code: 1d6n
9890908 G.P.Wang, C.Lundegaard, K.F.Jensen, and C.Grubmeyer (1999).
Kinetic mechanism of OMP synthase: a slow physical step following group transfer limits catalytic rate.
  Biochemistry, 38, 275-283.  
10090755 H.G.Schnizer, S.K.Boehlein, J.D.Stewart, N.G.Richards, and S.M.Schuster (1999).
Formation and isolation of a covalent intermediate during the glutaminase reaction of a class II amidotransferase.
  Biochemistry, 38, 3677-3682.  
10574791 I.I.Mathews, T.J.Kappock, J.Stubbe, and S.E.Ealick (1999).
Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway.
  Structure, 7, 1395-1406.
PDB codes: 1d7a 1qcz
10092838 J.P.Page, N.R.Munagala, and C.C.Wang (1999).
Point mutations in the guanine phosphoribosyltransferase from Giardia lamblia modulate pyrophosphate binding and enzyme catalysis.
  Eur J Biochem, 259, 565-571.  
10387047 M.K.Geck, and J.F.Kirsch (1999).
A novel, definitive test for substrate channeling illustrated with the aspartate aminotransferase/malate dehydrogenase system.
  Biochemistry, 38, 8032-8037.  
  10368157 P.Rappu, B.S.Shin, H.Zalkin, and P.Mäntsälä (1999).
A role for a highly conserved protein of unknown function in regulation of Bacillus subtilis purA by the purine repressor.
  J Bacteriol, 181, 3810-3815.  
  10049369 S.Li, J.L.Smith, and H.Zalkin (1999).
Mutational analysis of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase propeptide processing.
  J Bacteriol, 181, 1403-1408.  
10587437 T.M.Larsen, S.K.Boehlein, S.M.Schuster, N.G.Richards, J.B.Thoden, H.M.Holden, and I.Rayment (1999).
Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product.
  Biochemistry, 38, 16146-16157.
PDB code: 1ct9
9739095 A.Teplyakov, G.Obmolova, M.A.Badet-Denisot, B.Badet, and I.Polikarpov (1998).
Involvement of the C terminus in intramolecular nitrogen channeling in glucosamine 6-phosphate synthase: evidence from a 1.6 A crystal structure of the isomerase domain.
  Structure, 6, 1047-1055.
PDB code: 1moq
9689037 B.O.Bachmann, R.Li, and C.A.Townsend (1998).
beta-Lactam synthetase: a new biosynthetic enzyme.
  Proc Natl Acad Sci U S A, 95, 9082-9086.  
9551555 D.R.Tomchick, R.J.Turner, R.L.Switzer, and J.L.Smith (1998).
Adaptation of an enzyme to regulatory function: structure of Bacillus subtilis PyrR, a pyr RNA-binding attenuation protein and uracil phosphoribosyltransferase.
  Structure, 6, 337-350.
PDB codes: 1a3c 1a4x
9818189 F.M.Raushel, J.B.Thoden, G.D.Reinhart, and H.M.Holden (1998).
Carbamoyl phosphate synthetase: a crooked path from substrates to products.
  Curr Opin Chem Biol, 2, 624-632.  
9914247 H.M.Holden, J.B.Thoden, and F.M.Raushel (1998).
Carbamoyl phosphate synthetase: a tunnel runs through it.
  Curr Opin Struct Biol, 8, 679-685.  
9914248 J.L.Smith (1998).
Glutamine PRPP amidotransferase: snapshots of an enzyme in action.
  Curr Opin Struct Biol, 8, 686-694.  
9628859 M.A.Schumacher, D.Carter, D.M.Scott, D.S.Roos, B.Ullman, and R.G.Brennan (1998).
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.
  EMBO J, 17, 3219-3232.
PDB codes: 1bd3 1bd4 1upf 1upu
9753692 M.Rizzi, M.Bolognesi, and A.Coda (1998).
A novel deamido-NAD+-binding site revealed by the trapped NAD-adenylate intermediate in the NAD+ synthetase structure.
  Structure, 6, 1129-1140.
PDB code: 2nsy
9521725 N.R.Munagala, M.S.Chin, and C.C.Wang (1998).
Steady-state kinetics of the hypoxanthine-guanine-xanthine phosphoribosyltransferase from Tritrichomonas foetus: the role of threonine-47.
  Biochemistry, 37, 4045-4051.  
9860824 P.J.Focia, S.P.Craig, and A.E.Eakin (1998).
Approaching the transition state in the crystal structure of a phosphoribosyltransferase.
  Biochemistry, 37, 17120-17127.
PDB code: 1tc2
9790669 P.J.Focia, S.P.Craig, R.Nieves-Alicea, R.J.Fletterick, and A.E.Eakin (1998).
A 1.4 A crystal structure for the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi.
  Biochemistry, 37, 15066-15075.
PDB code: 1tc1
9862811 V.Sharma, C.Grubmeyer, and J.C.Sacchettini (1998).
Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target.
  Structure, 6, 1587-1599.
PDB codes: 1qpn 1qpo 1qpq 1qpr
9843369 W.Wang, T.J.Kappock, J.Stubbe, and S.E.Ealick (1998).
X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli.
  Biochemistry, 37, 15647-15662.
PDB code: 1gso
9521733 Y.Xu, and C.Grubmeyer (1998).
Catalysis in human hypoxanthine-guanine phosphoribosyltransferase: Asp 137 acts as a general acid/base.
  Biochemistry, 37, 4114-4124.  
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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