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
Q13423 NNTM_HUMAN NADPH + NAD(+) = NADP(+) + NADH. Homodimer (By similarity). Mitochondrion inner membrane, Multi-pass membrane protein, Matrix side (Potential).
P11024 NNTM_BOVIN NADPH + NAD(+) = NADP(+) + NADH. Homodimer. 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
15846
18009
16908
PubChem 5884
5893
5886
439153
1d4oA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
1djlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
1djlB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
1pt9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:TAP Unbound
1pt9B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:TAP Unbound
1u31A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
1u31B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 31;ARG 66;TYR 147
1djlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 890;ARG 925;TYR 1006
1djlB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 890;ARG 925;TYR 1006
1pt9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 54;ARG 89;TYR 170
1pt9B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 54;ARG 89;TYR 170
1u31A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 54;ARG 89;TYR 170
1u31B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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