ELFV_dehydrog

Glutamate/Leucine/Phenylalanine/Valine dehydrogenase

• SMART accession number: SM00839
• Description: Glutamate, leucine, phenylalanine and valine dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.
• Interpro abstract (IPR006096):

  Glutamate, leucine, phenylalanine and valine dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.

  Glutamate dehydrogenases (EC 1.4.1.2, EC 1.4.1.3, and EC 1.4.1.4) (GluDH) are enzymes that catalyse the NAD- and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate [(PUBMED:1358610), (PUBMED:8315654)]. GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction [(PUBMED:2989290)] - this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha- keto acids [(PUBMED:3368458)].

  Leucine dehydrogenase (EC 1.4.1.9) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues [(PUBMED:3069133)]. Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.

  Phenylalanine dehydrogenase (EC 1.4.1.20) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate [(PUBMED:1880121)].

  Valine dehydrogenase (EC 1.4.1.8) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate [(PUBMED:8320231)].

  This entry represents the C-terminal domain of these proteins.

• GO process: oxidation-reduction process (GO:0055114), cellular amino acid metabolic process (GO:0006520)
• GO function: oxidoreductase activity (GO:0016491)

There are 2347 ELFV_dehydrog domains in 2347 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: metabolism

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Baker PJ, Turnbull AP, Sedelnikova SE, Stillman TJ, Rice DW
• A role for quaternary structure in the substrate specificity of leucinedehydrogenase.
• Structure. 1995; 3: 693-705

BACKGROUND: Glutamate, phenylalanine and leucine dehydrogenases catalyzethe NAD(P)(+)-linked oxidative deamination of L-amino acids to thecorresponding 2-oxoacids, and sequence homology between these enzymesclearly indicates the existence of an enzyme superfamily related bydivergent evolution. We have undertaken structural studies on a number ofmembers of this family in order to investigate the molecular basis oftheir differential amino acid specificity. RESULTS: We have solved theX-ray structure of the leucine dehydrogenase from Bacillus sphaericus to aresolution of 2.2 A. Each subunit of this octameric enzyme contains 364amino acids and folds into two domains, separated by a deep cleft. Thenicotinamide ring of the NAD+ cofactor binds deep in this cleft, which isthought to close during the hydride transfer step of the catalytic cycle.CONCLUSIONS: Comparison of the structure of leucine dehydrogenase with ahexameric glutamate dehydrogenase has shown that these two enzymes share arelated fold and possess a similar catalytic chemistry. A mechanism forthe basis of the differential amino acid specificity between these enzymesinvolves point mutations in the amino acid side-chain specificity pocketand subtle changes in the shape of this pocket caused by the differencesin quaternary structure.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
31.27	map00251	Glutamate metabolism
31.27	map00910	Nitrogen metabolism
11.52	map00471	D-Glutamine and D-glutamate metabolism
11.52	map00330	Arginine and proline metabolism
6.84	map00280	Valine, leucine and isoleucine degradation
6.84	map00290	Valine, leucine and isoleucine biosynthesis
0.37	map00272	Cysteine metabolism
0.19	map00400	Phenylalanine, tyrosine and tryptophan biosynthesis
0.19	map00360	Phenylalanine metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with ELFV_dehydrog domain which could be assigned to a KEGG orthologous group, and not all proteins containing ELFV_dehydrog domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of ELFV_dehydrog domains in PDB

PDB code	Title
1aup	Glutamate dehydrogenase
1b26	Glutamate dehydrogenase
1b3b	Thermotoga maritima glutamate dehydrogenase mutant n97d, g376k
1bgv	Glutamate dehydrogenase
1bvu	Glutamate dehydrogenase from thermococcus litoralis
1bw9	Phenylalanine dehydrogenase structure in ternary complex with nad+ and phenylpyruvate
1bxg	Phenylalanine dehydrogenase structure in ternary complex with nad+ and beta-phenylpropionate
1c1d	L-phenylalanine dehydrogenase structure in ternary complex with nadh and l-phenylalanine
1c1x	L-phenylalanine dehydrogenase structure in ternary complex with nad+ and l-3-phenyllactate
1euz	Glutamate dehydrogenase from thermococcus profundus in the unligated state
1gtm	Structure of glutamate dehydrogenase
1hrd	Glutamate dehydrogenase
1hwx	Crystal structure of bovine liver glutamate dehydrogenase complexed with gtp, nadh, and l-glutamic acid
1hwy	Bovine glutamate dehydrogenase complexed with nad and 2- oxoglutarate
1hwz	Bovine glutamate dehydrogenase complexed with nadph, glutamate, and gtp
1k89	K89l mutant of glutamate dehydrogenase
1l1f	Structure of human glutamate dehydrogenase-apo form
1leh	Leucine dehydrogenase from bacillus sphaericus
1nqt	Crystal structure of bovine glutamate dehydrogenase-adp complex
1nr1	Crystal structure of the r463a mutant of human glutamate dehydrogenase
1nr7	Crystal structure of apo bovine glutamate dehydrogenase
1v9l	L-glutamate dehydrogenase from pyrobaculum islandicum complexed with nad
2bma	The crystal structure of plasmodium falciparum glutamate dehydrogenase, a putative target for novel antimalarial drugs
2tmg	Thermotoga maritima glutamate dehydrogenase mutant s128r, t158e, n117r, s160e
3etd	Structure of glutamate dehydrogenase complexed with bithionol
3ete	Crystal structure of bovine glutamate dehydrogenase complexed with hexachlorophene
3etg	Glutamate dehydrogenase complexed with gw5074

Links (links to other resources describing this domain)

• PFAM: ELFV_dehydrog
• INTERPRO: IPR006096