DB code: M00162

CATH domain -.-.-.- :
-.-.-.- :
-.-.-.- :
3.40.50.1220 : Rossmann fold Catalytic domain
E.C. 1.6.1.2
CSA 1djl
M-CSA 1djl
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1220 : Rossmann fold M00161 T00237 T00230

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P11024 NAD(P) transhydrogenase, mitochondrial
EC 1.6.1.2
Nicotinamide nucleotide transhydrogenase
Pyridine nucleotide transhydrogenase
NP_776368.1 (Protein)
NM_173943.3 (DNA/RNA sequence)
PF01262 (AlaDh_PNT_C)
PF05222 (AlaDh_PNT_N)
PF12769 (DUF3814)
PF02233 (PNTB)
[Graphical View]
Q13423 NAD(P) transhydrogenase, mitochondrial
EC 1.6.1.2
Nicotinamide nucleotide transhydrogenase
Pyridine nucleotide transhydrogenase
NP_036475.3 (Protein)
NM_012343.3 (DNA/RNA sequence)
NP_892022.2 (Protein)
NM_182977.2 (DNA/RNA sequence)
PF01262 (AlaDh_PNT_C)
PF05222 (AlaDh_PNT_N)
PF12769 (DUF3814)
PF02233 (PNTB)
[Graphical View]

KEGG enzyme name
NAD(P)+ transhydrogenase (AB-specific)
pyridine nucleotide transhydrogenase
transhydrogenase
NAD(P)+ transhydrogenase
nicotinamide adenine dinucleotide (phosphate) transhydrogenase
NAD+ transhydrogenase
NADH transhydrogenase
nicotinamide nucleotide transhydrogenase
NADPH-NAD+ transhydrogenase
pyridine nucleotide transferase
NADPH-NAD+ oxidoreductase
NADH-NADP+-transhydrogenase
NADPH:NAD+ transhydrogenase
H+-Thase
energy-linked transhydrogenase
NAD(P)+ transhydrogenase (AB-specific)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P11024 NNTM_BOVIN NADPH + NAD(+) = NADP(+) + NADH. Homodimer. Mitochondrion inner membrane, Multi-pass membrane protein, Matrix side (Potential).
Q13423 NNTM_HUMAN NADPH + NAD(+) = NADP(+) + NADH. Homodimer (By similarity). Mitochondrion inner membrane, Multi-pass membrane protein, Matrix side (Potential).

KEGG Pathways
Map code Pathways E.C.
MAP00760 Nicotinate and nicotinamide metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00005 C00003 C00006 C00004
E.C.
Compound NADPH NAD+ NADP+ NADH
Type amide group,amine group,nucleotide amide group,amine group,nucleotide amide group,amine group,nucleotide amide group,amine group,nucleotide
ChEBI 16474
 16474
 		15846
 15846
 		18009
 18009
 		16908
 16908
PubChem 5884
 5884
 		5893
 5893
 		5886
 5886
 		439153
 439153
1d4oA Unbound Unbound Bound:NAP Unbound
1djlA Unbound Unbound Bound:NAP Unbound
1djlB Unbound Unbound Bound:NAP Unbound
1pt9A Unbound Unbound Analogue:TAP Unbound
1pt9B Unbound Unbound Analogue:TAP Unbound
1u31A Unbound Unbound Bound:NAP Unbound
1u31B Unbound Unbound Bound:NAP Unbound

Reference for Active-site residues
resource references E.C.
literature [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1d4oA TYR 31;ARG 66;TYR 147
1djlA TYR 890;ARG 925;TYR 1006
1djlB TYR 890;ARG 925;TYR 1006
1pt9A TYR 54;ARG 89;TYR 170
1pt9B TYR 54;ARG 89;TYR 170
1u31A TYR 54;ARG 89;TYR 170
1u31B TYR 54;ARG 89;TYR 170

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[8]
p.8-9
[10]
[11]

References
[1]
Resource
Comments
Medline ID
PubMed ID 2361137
Journal Biochemistry
Year 1990
Volume 29
Pages 4136-43
Authors Yamaguchi M, Wakabayashi S, Hatefi Y
Title Mitochondrial energy-linked nicotinamide nucleotide transhydrogenase: effect of substrates on the sensitivity of the enzyme to trypsin and identification of tryptic cleavage sites.
Related PDB
Related UniProtKB
[2]
Resource
Comments TOPOLOGY.
Medline ID 91170247
PubMed ID 2005110
Journal J Biol Chem
Year 1991
Volume 266
Pages 5728-35
Authors Yamaguchi M, Hatefi Y
Title Mitochondrial energy-linked nicotinamide nucleotide transhydrogenase. Membrane topography of the bovine enzyme.
Related PDB
Related UniProtKB P11024
[3]
Resource
Comments
Medline ID
PubMed ID 10514549
Journal Biochim Biophys Acta
Year 1999
Volume 1413
Pages 81-91
Authors Peake SJ, Venning JD, Cotton NP, Jackson JB
Title Evidence for the stabilization of NADPH relative to NADP(+) on the dIII components of proton-translocating transhydrogenases from Homo sapiens and from Rhodospirillum rubrum by measurement of tryptophan fluorescence.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10216162
Journal Biochim Biophys Acta
Year 1999
Volume 1411
Pages 159-69
Authors Peake SJ, Venning JD, Jackson JB
Title A catalytically active complex formed from the recombinant dI protein of Rhodospirillum rubrum transhydrogenase, and the recombinant dIII protein of the human enzyme.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10587945
Journal Microb Comp Genomics
Year 1999
Volume 4
Pages 173-86
Authors Studley WK, Yamaguchi M, Hatefi Y, Saier MH Jr
Title Phylogenetic analyses of proton-translocating transhydrogenases.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 903-1086.
Medline ID 20051009
PubMed ID 10581554
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 1126-31
Authors Prasad GS, Sridhar V, Yamaguchi M, Hatefi Y, Stout CD
Title Crystal structure of transhydrogenase domain III at 1.2 A resolution.
Related PDB 1d4o
Related UniProtKB P11024
[7]
Resource
Comments
Medline ID
PubMed ID 10611473
Journal FEBS Lett
Year 1999
Volume 464
Pages 1-8
Authors Jackson JB, Peake SJ, White SA
Title Structure and mechanism of proton-translocating transhydrogenase.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 880-1086.
Medline ID 20139687
PubMed ID 10673423
Journal Structure Fold Des
Year 2000
Volume 8
Pages 1-12
Authors White SA, Peake SJ, McSweeney S, Leonard G, Cotton NP, Jackson JB
Title The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria.
Related PDB 1djl
Related UniProtKB Q13423
[9]
Resource
Comments
Medline ID
PubMed ID 11231296
Journal Eur J Biochem
Year 2001
Volume 268
Pages 1430-8
Authors Rodrigues DJ, Venning JD, Quirk PG, Jackson JB
Title A change in ionization of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase regulates both hydride transfer and nucleotide release.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12791694
Journal J Biol Chem
Year 2003
Volume 278
Pages 33208-16
Authors Singh A, Venning JD, Quirk PG, van Boxel GI, Rodrigues DJ, White SA, Jackson JB
Title Interactions between transhydrogenase and thio-nicotinamide Analogues of NAD(H) and NADP(H) underline the importance of nucleotide conformational changes in coupling to proton translocation.
Related PDB 1pt9 1ptj
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 15323555
Journal Biochemistry
Year 2004
Volume 43
Pages 10952-64
Authors Mather OC, Singh A, van Boxel GI, White SA, Jackson JB
Title Active-site conformational changes associated with hydride transfer in proton-translocating transhydrogenase.
Related PDB 1u28 1u2d 1u2g 1u31
Related UniProtKB

Comments
This enzyme is composed of three domains, N-terminal matrix domain, membrane-intercalated domain with proton channel, and C-terminal matrix domain. Although the structures for the C-terminal domain has been solved, those of the other domains have not been determined yet. However, the N-terminal domain seems to be homologous to the alpha-1 subunit of the counterpart of bacterial enzyme (Swiss-prot;Q60164).

Created Updated
2004-12-17 2009-02-26