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Oxidoreductase PDB id
1bgv
Jmol
Contents
Protein chain
449 a.a. *
Ligands
GLU
Waters ×217
* Residue conservation analysis
PDB id:
1bgv
Name: Oxidoreductase
Title: Glutamate dehydrogenase
Structure: Glutamate dehydrogenase. Chain: a. Other_details: the residue labelled b 501, a glutamate, is enzyme's substrate which is bound within the active site. Is thought to an only partially occupied site and so its oc was set to 0.53.
Source: Clostridium symbiosum. Organism_taxid: 1512
Biol. unit: Homo-Hexamer (from PDB file)
Resolution:
1.90Å     R-factor:   0.173    
Authors: T.J.Stillman,P.J.Baker,K.L.Britton,D.W.Rice
Key ref: T.J.Stillman et al. (1993). Conformational flexibility in glutamate dehydrogenase. Role of water in substrate recognition and catalysis. J Mol Biol, 234, 1131-1139. PubMed id: 8263917 DOI: 10.1006/jmbi.1993.1665
Date:
01-Jun-98     Release date:   14-Oct-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24295  (DHE2_CLOSY) -  NAD-specific glutamate dehydrogenase
Seq:
Struc: 		450 a.a.
449 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.4.1.2  - Glutamate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-glutamate + H2O + NAD+ = 2-oxoglutarate + NH3 + NADH
L-glutamate
Bound ligand (Het Group name = GLU)
corresponds exactly 		+ H(2)O
 + NAD(+)
 = 2-oxoglutarate
 + NH(3)
 + NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     nucleotide binding     4 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1993.1665 J Mol Biol 234:1131-1139 (1993)
PubMed id: 8263917  
 
 
Conformational flexibility in glutamate dehydrogenase. Role of water in substrate recognition and catalysis.
T.J.Stillman, P.J.Baker, K.L.Britton, D.W.Rice.
 
  ABSTRACT  
 
We have solved the structure of the binary complex of the glutamate dehydrogenase from Clostridium symbiosum with glutamate to 1.9 A resolution. In this complex, the glutamate side-chain lies in a pocket on the enzyme surface and a key determinant of the enzymic specificity is an interaction of the substrate gamma-carboxyl group with the amino group of Lys89. In the apo-enzyme, Lys113 from the catalytic domain forms an important hydrogen bond to Asn373, in the NAD(+)-binding domain. On glutamate binding, the side-chain of this lysine undergoes a significant movement in order to optimize its hydrogen bonding to the alpha-carboxyl group of the substrate. Despite this shift, the interaction between Lys113 and Asn373 is maintained by a large-scale conformational change that closes the cleft between the two domains. Modelling studies indicate that in this "closed" conformation the C-4 of the nicotinamide ring and the alpha-carbon atom of the amino acid substrate are poised for efficient hydride transfer. Examination of the structure has led to a proposal for the catalytic activity of the enzyme, which involves Asp165 as a general base, and an enzyme-bound water molecule, hydrogen-bonded to an uncharged lysine residue, Lys125, as an attacking nucleophile in the reaction.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21428913 P.C.Engel (2011).
Making biochemistry count: life among the amino acid dehydrogenases.
  Biochem Soc Trans, 39, 425-429.  
20332210 K.Zhang, H.Li, K.M.Cho, and J.C.Liao (2010).
Expanding metabolism for total biosynthesis of the nonnatural amino acid L-homoalanine.
  Proc Natl Acad Sci U S A, 107, 6234-6239.  
20378971 R.Kawakami, M.Oyama, H.Sakuraba, and T.Ohshima (2010).
The unique kinetic behavior of the very large NAD-dependent glutamate dehydrogenase from Janthinobacterium lividum.
  Biosci Biotechnol Biochem, 74, 884-887.  
20829287 T.Tomita, T.Miyazaki, J.Miyazaki, T.Kuzuyama, and M.Nishiyama (2010).
Hetero-oligomeric glutamate dehydrogenase from Thermus thermophilus.
  Microbiology, 156, 3801-3813.  
19924903 H.F.Fisher, S.J.Maniscalco, J.Tally, and K.Tabanor (2009).
Application of the second rule of transient-state kinetic isotope effects to an enzymatic mechanism.
  Biochemistry, 48, 12265-12271.  
19504041 I.S.Pienaar, T.Schallert, S.Hattingh, and W.M.Daniels (2009).
Behavioral and quantitative mitochondrial proteome analyses of the effects of simvastatin: implications for models of neural degeneration.
  J Neural Transm, 116, 791-806.  
19531491 M.Li, C.J.Smith, M.T.Walker, and T.J.Smith (2009).
Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics.
  J Biol Chem, 284, 22988-23000.
PDB codes: 3etd 3ete 3etg
19270409 S.Tachibana, Y.Kuwamori, and Y.Asano (2009).
Discrimination of aliphatic substrates by a single amino acid substitution in Bacillus badius and Bacillus sphaericus phenylalanine dehydrogenases.
  Biosci Biotechnol Biochem, 73, 729-732.  
18491387 S.M.Tripathi, and R.Ramachandran (2008).
Crystal structures of the Mycobacterium tuberculosis secretory antigen alanine dehydrogenase (Rv2780) in apo and ternary complex forms captures "open" and "closed" enzyme conformations.
  Proteins, 72, 1089-1095.
PDB codes: 2voe 2voj
  18453703 S.M.Tripathi, and R.Ramachandran (2008).
Overexpression, purification, crystallization and preliminary X-ray analysis of Rv2780 from Mycobacterium tuberculosis H37Rv.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 367-370.  
18819805 T.J.Smith, and C.A.Stanley (2008).
Untangling the glutamate dehydrogenase allosteric nightmare.
  Trends Biochem Sci, 33, 557-564.  
17526698 R.Kawakami, H.Sakuraba, and T.Ohshima (2007).
Gene cloning and characterization of the very large NAD-dependent l-glutamate dehydrogenase from the psychrophile Janthinobacterium lividum, isolated from cold soil.
  J Bacteriol, 189, 5626-5633.  
16195607 I.H.Khan, H.Kim, H.Ashida, T.Ishikawa, H.Shibata, and Y.Sawa (2005).
Altering the substrate specificity of glutamate dehydrogenase from Bacillus subtilis by site-directed mutagenesis.
  Biosci Biotechnol Biochem, 69, 1802-1805.  
16244435 M.I.Khan, K.Ito, H.Kim, H.Ashida, T.Ishikawa, H.Shibata, and Y.Sawa (2005).
Molecular properties and enhancement of thermostability by random mutagenesis of glutamate dehydrogenase from Bacillus subtilis.
  Biosci Biotechnol Biochem, 69, 1861-1870.  
15139817 B.Jayaram, and T.Jain (2004).
The role of water in protein-DNA recognition.
  Annu Rev Biophys Biomol Struct, 33, 343-361.  
14530390 O.Millet, R.P.Hudson, and L.E.Kay (2003).
The energetic cost of domain reorientation in maltose-binding protein as studied by NMR and fluorescence spectroscopy.
  Proc Natl Acad Sci U S A, 100, 12700-12705.  
12414808 S.Aghajanian, M.Hovsepyan, K.F.Geoghegan, B.A.Chrunyk, and P.C.Engel (2003).
A thermally sensitive loop in clostridial glutamate dehydrogenase detected by limited proteolysis.
  J Biol Chem, 278, 1067-1074.  
14622249 S.Y.Seah, K.L.Britton, D.W.Rice, Y.Asano, and P.C.Engel (2003).
Kinetic analysis of phenylalanine dehydrogenase mutants designed for aliphatic amino acid dehydrogenase activity with guidance from homology-based modelling.
  Eur J Biochem, 270, 4628-4634.  
12193607 H.Y.Yoon, E.H.Cho, H.Y.Kwon, S.Y.Choi, and S.W.Cho (2002).
Importance of glutamate 279 for the coenzyme binding of human glutamate dehydrogenase.
  J Biol Chem, 277, 41448-41454.  
12220195 J.F.Tally, S.J.Maniscalco, S.K.Saha, and H.F.Fisher (2002).
Detection of multiple active site domain motions in transient-state component time courses of the Clostridium symbiosum L-glutamate dehydrogenase-catalyzed oxidative deamination reaction.
  Biochemistry, 41, 11284-11293.  
12037317 T.A.Muranova, S.N.Ruzheinikov, S.E.Sedelnikova, P.J.Baker, A.Pasquo, A.Galkin, N.Esaki, T.Ohshima, K.Soda, and D.W.Rice (2002).
Crystallization and preliminary X-ray analysis of substrate complexes of leucine dehydrogenase from Thermoactinomyces intermedius.
  Acta Crystallogr D Biol Crystallogr, 58, 1059-1062.  
11231268 B.M.Hayden, and P.C.Engel (2001).
Construction, separation and properties of hybrid hexamers of glutamate dehydrogenase in which five of the six subunits are contributed by the catalytically inert D165S.
  Eur J Biochem, 268, 1173-1180.  
11258921 M.Nakasako, T.Fujisawa, S.Adachi, T.Kudo, and S.Higuchi (2001).
Large-scale domain movements and hydration structure changes in the active-site cleft of unligated glutamate dehydrogenase from Thermococcus profundus studied by cryogenic X-ray crystal structure analysis and small-angle X-ray scattering.
  Biochemistry, 40, 3069-3079.
PDB code: 1euz
11722565 X.G.Wang, K.L.Britton, T.J.Stillman, D.W.Rice, and P.C.Engel (2001).
Conversion of a glutamate dehydrogenase into methionine/norleucine dehydrogenase by site-directed mutagenesis.
  Eur J Biochem, 268, 5791-5799.  
10742211 L.Rijnen, P.Courtin, J.C.Gripon, and M.Yvon (2000).
Expression of a heterologous glutamate dehydrogenase gene in Lactococcus lactis highly improves the conversion of amino acids to aroma compounds.
  Appl Environ Microbiol, 66, 1354-1359.  
  11106178 M.Cirilli, G.Scapin, A.Sutherland, J.C.Vederas, and J.S.Blanchard (2000).
The three-dimensional structure of the ternary complex of Corynebacterium glutamicum diaminopimelate dehydrogenase-NADPH-L-2-amino-6-methylene-pimelate.
  Protein Sci, 9, 2034-2037.
PDB code: 1f06
10924111 N.M.Brunhuber, J.B.Thoden, J.S.Blanchard, and J.L.Vanhooke (2000).
Rhodococcus L-phenylalanine dehydrogenase: kinetics, mechanism, and structural basis for catalytic specificity.
  Biochemistry, 39, 9174-9187.
PDB codes: 1c1d 1c1x
10601858 R.Di Fraia, V.Wilquet, M.A.Ciardiello, V.Carratore, A.Antignani, L.Camardella, N.Glansdorff, and G.Di Prisco (2000).
NADP+-dependent glutamate dehydrogenase in the Antarctic psychrotolerant bacterium Psychrobacter sp. TAD1. Characterization, protein and DNA sequence, and relationship to other glutamate dehydrogenases.
  Eur J Biochem, 267, 121-131.  
10707024 S.Kumar, B.Ma, C.J.Tsai, and R.Nussinov (2000).
Electrostatic strengths of salt bridges in thermophilic and mesophilic glutamate dehydrogenase monomers.
  Proteins, 38, 368-383.  
  10801498 S.Suresh, S.Turley, F.R.Opperdoes, P.A.Michels, and W.G.Hol (2000).
A potential target enzyme for trypanocidal drugs revealed by the crystal structure of NAD-dependent glycerol-3-phosphate dehydrogenase from Leishmania mexicana.
  Structure, 8, 541-552.
PDB codes: 1evy 1evz
10029526 J.L.Vanhooke, J.B.Thoden, N.M.Brunhuber, J.S.Blanchard, and H.M.Holden (1999).
Phenylalanine dehydrogenase from Rhodococcus sp. M4: high-resolution X-ray analyses of inhibitory ternary complexes reveal key features in the oxidative deamination mechanism.
  Biochemistry, 38, 2326-2339.
PDB codes: 1bw9 1bxg
  10425679 P.E.Peterson, and T.J.Smith (1999).
The structure of bovine glutamate dehydrogenase provides insights into the mechanism of allostery.
  Structure, 7, 769-782.
PDB codes: 1ch6 1hwx 3mw9
  10211832 S.Aghajanian, T.P.Walsh, and P.C.Engel (1999).
Specificity of coenzyme analogues and fragments in promoting or impeding the refolding of clostridial glutamate dehydrogenase.
  Protein Sci, 8, 866-872.  
10450084 S.Hayward (1999).
Structural principles governing domain motions in proteins.
  Proteins, 36, 425-435.  
10531494 S.Higuchi, M.Nakasako, and T.Kudo (1999).
Crystallization and preliminary x-ray diffraction studies of hyperthermostable glutamate dehydrogenase from Thermococcus profundus.
  Acta Crystallogr D Biol Crystallogr, 55, 1917-1919.  
9761891 A.Pasquo, K.L.Britton, P.J.Baker, G.Brearley, R.J.Hinton, A.J.Moir, T.J.Stillman, and D.W.Rice (1998).
Crystallization of NAD+-dependent phenylalanine dehydrogenase from Nocardia sp239.
  Acta Crystallogr D Biol Crystallogr, 54, 269-272.  
  9829940 B.R.Belitsky, and A.L.Sonenshein (1998).
Role and regulation of Bacillus subtilis glutamate dehydrogenase genes.
  J Bacteriol, 180, 6298-6305.  
9770481 C.Vetriani, D.L.Maeder, N.Tolliday, K.S.Yip, T.J.Stillman, K.L.Britton, D.W.Rice, H.H.Klump, and F.T.Robb (1998).
Protein thermostability above 100 degreesC: a key role for ionic interactions.
  Proc Natl Acad Sci U S A, 95, 12300-12305.  
9521647 G.Scapin, M.Cirilli, S.G.Reddy, Y.Gao, J.C.Vederas, and J.S.Blanchard (1998).
Substrate and inhibitor binding sites in Corynebacterium glutamicum diaminopimelate dehydrogenase.
  Biochemistry, 37, 3278-3285.
PDB codes: 2dap 3dap
9535890 K.L.Britton, T.J.Stillman, K.S.Yip, P.Forterre, P.C.Engel, and D.W.Rice (1998).
Insights into the molecular basis of salt tolerance from the study of glutamate dehydrogenase from Halobacterium salinarum.
  J Biol Chem, 273, 9023-9030.  
9665174 K.L.Britton, Y.Asano, and D.W.Rice (1998).
Crystal structure and active site location of N-(1-D-carboxylethyl)-L-norvaline dehydrogenase.
  Nat Struct Biol, 5, 593-601.
PDB code: 1bg6
9893953 R.Scandurra, V.Consalvi, R.Chiaraluce, L.Politi, and P.C.Engel (1998).
Protein thermostability in extremophiles.
  Biochimie, 80, 933-941.  
9312120 A.P.Turnbull, P.J.Baker, and D.W.Rice (1997).
Analysis of the quaternary structure, substrate specificity, and catalytic mechanism of valine dehydrogenase.
  J Biol Chem, 272, 25105-25111.  
8999934 D.Delforge, B.Devreese, M.Dieu, E.Delaive, J.Van Beeumen, and J.Remacle (1997).
Identification of lysine 74 in the pyruvate binding site of alanine dehydrogenase from Bacillus subtilis. Chemical modification with 2,4,6-trinitrobenzenesulfonic acid, n-succinimidyl 3-(2-pyridyldithio)propionate, and 5'-(p-(fluorosulfonyl)benzoyl)adenosine.
  J Biol Chem, 272, 2276-2284.  
8639325 D.W.Rice, K.S.Yip, T.J.Stillman, K.L.Britton, A.Fuentes, I.Connerton, A.Pasquo, R.Scandura, and P.C.Engel (1996).
Insights into the molecular basis of thermal stability from the structure determination of Pyrococcus furiosus glutamate dehydrogenase.
  FEMS Microbiol Rev, 18, 105-117.  
8885833 G.Scapin, S.G.Reddy, and J.S.Blanchard (1996).
Three-dimensional structure of meso-diaminopimelic acid dehydrogenase from Corynebacterium glutamicum.
  Biochemistry, 35, 13540-13551.
PDB code: 1dap
8555203 S.J.Maniscalco, S.K.Saha, P.Vicedomine, and H.F.Fisher (1996).
A difference in the sequence of steps in the reactions catalyzed by two closely homologous forms of glutamate dehydrogenase.
  Biochemistry, 35, 89-94.  
8987981 S.K.Saha, S.J.Maniscalco, and H.F.Fisher (1996).
Mechanistic interpretation of tryptophan fluorescence quenching in the time courses of glutamate dehydrogenase catalyzed reactions.
  Biochemistry, 35, 16483-16488.  
9116050 S.W.Cho, and J.E.Lee (1996).
Modification of brain glutamate dehydrogenase isoproteins with pyridoxal 5'-phosphate.
  Biochimie, 78, 817-821.  
7893717 C.L.Careaga, J.Sutherland, J.Sabeti, and J.J.Falke (1995).
Large amplitude twisting motions of an interdomain hinge: a disulfide trapping study of the galactose-glucose binding protein.
  Biochemistry, 34, 3048-3055.  
7758464 K.L.Britton, P.J.Baker, K.M.Borges, P.C.Engel, A.Pasquo, D.W.Rice, F.T.Robb, R.Scandurra, T.J.Stillman, and K.S.Yip (1995).
Insights into thermal stability from a comparison of the glutamate dehydrogenases from Pyrococcus furiosus and Thermococcus litoralis.
  Eur J Biochem, 229, 688-695.  
  8591026 K.S.Yip, T.J.Stillman, K.L.Britton, P.J.Artymiuk, P.J.Baker, S.E.Sedelnikova, P.C.Engel, A.Pasquo, R.Chiaraluce, and V.Consalvi (1995).
The structure of Pyrococcus furiosus glutamate dehydrogenase reveals a key role for ion-pair networks in maintaining enzyme stability at extreme temperatures.
  Structure, 3, 1147-1158.
PDB codes: 1gtm 1hrd
8536710 L.A.Basso, P.C.Engel, and A.R.Walmsley (1995).
The mechanism of substrate and coenzyme binding to clostridial glutamate dehydrogenase during reductive amination.
  Eur J Biochem, 234, 603-615.  
  8591046 P.J.Baker, A.P.Turnbull, S.E.Sedelnikova, T.J.Stillman, and D.W.Rice (1995).
A role for quaternary structure in the substrate specificity of leucine dehydrogenase.
  Structure, 3, 693-705.
PDB code: 1leh
  7705101 N.M.Brunhuber, and J.S.Blanchard (1994).
The biochemistry and enzymology of amino acid dehydrogenases.
  Crit Rev Biochem Mol Biol, 29, 415-467.  
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.