DB code: M00161

CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
3.40.50.1770 : Rossmann fold Catalytic domain
-.-.-.- :
3.40.50.1220 : Rossmann fold Catalytic domain
E.C. 1.6.1.2
CSA
M-CSA
MACiE M0116

CATH domain Related DB codes (homologues)
3.40.50.1220 : Rossmann fold M00162 T00237 T00230
3.40.50.1770 : Rossmann fold D00031
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00319 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q2RSB2 NAD(P) transhydrogenase subunit alpha part 1
EC 1.6.1.2
Nicotinamide nucleotide transhydrogenase subunit alpha 1
Pyridine nucleotide transhydrogenase subunit alpha 1
Proton-translocating transhydrogenase component 1
dI
YP_427270.1 (Protein)
NC_007643.1 (DNA/RNA sequence)
PF01262 (AlaDh_PNT_C)
PF05222 (AlaDh_PNT_N)
[Graphical View]
Q2RSB3 NAD(P) transhydrogenase subunit alpha part 2
EC 1.6.1.2
Nicotinamide nucleotide transhydrogenase subunit alpha 2
Pyridine nucleotide transhydrogenase subunit alpha 2
Proton-translocating transhydrogenase component 2
dII
YP_427269.1 (Protein)
NC_007643.1 (DNA/RNA sequence)
PF12769 (DUF3814)
[Graphical View]
Q2RSB4 NAD(P) transhydrogenase subunit beta
EC 1.6.1.2
Nicotinamide nucleotide transhydrogenase subunit beta
Pyridine nucleotide transhydrogenase subunit beta
Proton-translocating transhydrogenase NADP(H)-binding component
dIII
YP_427268.1 (Protein)
NC_007643.1 (DNA/RNA sequence)
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
Q2RSB2 PNTAA_RHORT NADPH + NAD(+) = NADP(+) + NADH. Complex of an alpha and a beta chain, in Rhodospirillum, the alpha chain seems to be made of two subunits (By similarity).
Q2RSB3 PNTAB_RHORT NADPH + NAD(+) = NADP(+) + NADH. Complex of an alpha and a beta chain, in Rhodospirillum, the alpha chain seems to be made of two subunits (By similarity). Cell inner membrane, Multi-pass membrane protein (By similarity).
Q2RSB4 PNTB_RHORT NADPH + NAD(+) = NADP(+) + NADH. Complex of an alpha and a beta chain, in Rhodospirillum, the alpha chain seems to be made of two subunits (By similarity). Cell inner membrane, Multi-pass membrane protein (By similarity).

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
1f8gA01 Unbound Bound:NAD Unbound Unbound
1f8gB01 Unbound Analogue:NAD Unbound Unbound
1f8gC01 Unbound Analogue:NAD Unbound Unbound
1f8gD01 Unbound Bound:NAD Unbound Unbound
1l7dA01 Unbound Unbound Unbound Unbound
1l7dB01 Unbound Unbound Unbound Unbound
1l7dC01 Unbound Unbound Unbound Unbound
1l7dD01 Unbound Unbound Unbound Unbound
1l7eA01 Unbound Unbound Unbound Bound:NAI
1l7eB01 Unbound Unbound Unbound Unbound
1l7eC01 Unbound Unbound Unbound Unbound
1l7eD01 Unbound Unbound Unbound Bound:NAI
1hzzA01 Unbound Bound:NAD Unbound Unbound
1hzzB01 Unbound Unbound Unbound Unbound
1nm5A01 Unbound Bound:NAD Unbound Unbound
1nm5B01 Unbound Analogue:NAD Unbound Unbound
1ptjA01 Unbound Unbound Unbound Unbound
1ptjB01 Unbound Analogue:SND Unbound Unbound
1u28A01 Unbound Bound:NAD Unbound Unbound
1u28B01 Unbound Analogue:NAD Unbound Unbound
1u2dA01 Unbound Bound:NAD Unbound Unbound
1u2dB01 Unbound Bound:NAD Unbound Unbound
1u2gA01 Unbound Analogue:APR Unbound Unbound
1u2gB01 Unbound Analogue:APR Unbound Unbound
1f8gA02 Unbound Unbound Unbound Unbound
1f8gB02 Unbound Unbound Unbound Unbound
1f8gC02 Unbound Unbound Unbound Unbound
1f8gD02 Unbound Unbound Unbound Unbound
1l7dA02 Unbound Unbound Unbound Unbound
1l7dB02 Unbound Unbound Unbound Unbound
1l7dC02 Unbound Unbound Unbound Unbound
1l7dD02 Unbound Unbound Unbound Unbound
1l7eA02 Unbound Unbound Unbound Unbound
1l7eB02 Unbound Unbound Unbound Unbound
1l7eC02 Unbound Unbound Unbound Unbound
1l7eD02 Unbound Unbound Unbound Unbound
1hzzA02 Unbound Unbound Unbound Unbound
1hzzB02 Unbound Unbound Unbound Unbound
1nm5A02 Unbound Unbound Unbound Unbound
1nm5B02 Unbound Unbound Unbound Unbound
1ptjA02 Unbound Unbound Unbound Unbound
1ptjB02 Unbound Unbound Unbound Unbound
1u28A02 Unbound Unbound Unbound Unbound
1u28B02 Unbound Unbound Unbound Unbound
1u2dA02 Unbound Unbound Unbound Unbound
1u2dB02 Unbound Unbound Unbound Unbound
1u2gA02 Unbound Unbound Unbound Unbound
1u2gB02 Unbound Unbound Unbound Unbound
1e3tA Unbound Unbound Bound:NAP Unbound
1pnoA Unbound Unbound Bound:NAP Unbound
1pnoB Unbound Unbound Bound:NAP Unbound
1pnqA Bound:NDP Unbound Unbound Unbound
1pnqB Bound:NDP Unbound Unbound Unbound
1hzzC Unbound Unbound Bound:NAP Unbound
1nm5C Unbound Unbound Bound:NAP Unbound
1ptjC Unbound Unbound Bound:NAP Unbound
1u28C Unbound Unbound Bound:NAP Unbound
1u2dC Bound:NDP Unbound Unbound Unbound
1u2gC Bound:NDP Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [6], [10] & [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1f8gA01 TYR 235
1f8gB01 TYR 235
1f8gC01 TYR 235
1f8gD01 TYR 235
1l7dA01 invisible Y235
1l7dB01 invisible Y235
1l7dC01 invisible Y235
1l7dD01 invisible Y235
1l7eA01 TYR 235
1l7eB01 invisible Y635
1l7eC01 invisible Y1035
1l7eD01 TYR 1435
1hzzA01 TYR 235
1hzzB01 invisible Y235
1nm5A01 invisible Y235
1nm5B01 invisible Y235
1ptjA01 TYR 235
1ptjB01 invisible Y235
1u28A01 TYR 235
1u28B01 invisible Y235
1u2dA01 TYR 235
1u2dB01 TYR 235
1u2gA01 TYR 235
1u2gB01 invisible Y235
1f8gA02 ARG 127;GLN 132;ASP 135;SER 138
1f8gB02 ARG 127;GLN 132;ASP 135;SER 138
1f8gC02 ARG 127;GLN 132;ASP 135;SER 138
1f8gD02 ARG 127;GLN 132;ASP 135;SER 138
1l7dA02 ARG 127;GLN 132;ASP 135;SER 138
1l7dB02 ARG 527;GLN 532;ASP 535;SER 538
1l7dC02 ARG 927;GLN 932;ASP 935;SER 938
1l7dD02 ARG 1327;GLN 1332;ASP 1335;SER 1338
1l7eA02 ARG 127;GLN 132;ASP 135;SER 138
1l7eB02 ARG 527;GLN 532;ASP 535;SER 538
1l7eC02 ARG 927;GLN 932;ASP 935;SER 938
1l7eD02 ARG 1327;GLN 1332;ASP 1335;SER 1338
1hzzA02 ARG 127;GLN 132;ASP 135;SER 138
1hzzB02 ARG 127;GLN 132;ASP 135;SER 138
1nm5A02 ARG 127;;ASP 135;SER 138 mutant Q132N
1nm5B02 ARG 127;;ASP 135;SER 138 mutant Q132N
1ptjA02 ARG 127;GLN 132;ASP 135;SER 138
1ptjB02 ARG 127;GLN 132;ASP 135;SER 138
1u28A02 ARG 127;GLN 132;ASP 135;SER 138
1u28B02 ARG 127;GLN 132;ASP 135;SER 138
1u2dA02 ARG 127;GLN 132;ASP 135;SER 138
1u2dB02 ARG 127;GLN 132;ASP 135;SER 138
1u2gA02 ARG 127;GLN 132;ASP 135;SER 138
1u2gB02 ARG 127;GLN 132;ASP 135;SER 138
1e3tA TYR 55;ARG 90;TYR 171
1pnoA TYR 316;ARG 351;TYR 432
1pnoB TYR 316;ARG 351;TYR 432
1pnqA TYR 316;ARG 351;TYR 432
1pnqB TYR 316;ARG 351;TYR 432
1hzzC TYR 55;ARG 90;TYR 171
1nm5C TYR 55;ARG 90;TYR 171
1ptjC TYR 55;ARG 90;TYR 171
1u28C TYR 55;ARG 90;TYR 171
1u2dC TYR 55;ARG 90;TYR 171
1u2gC TYR 55;ARG 90;TYR 171

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
p.5-6
[10]
p.813
[12]
p.44759-44760
[13]
p.30684-30685
[14]
p.167-173
[16]
[17]
Fig.8, p.12152
[18]
p.1223-1225
[19]
[21]
[22]

References
[1]
Resource
Comments
Medline ID
PubMed ID 8011636
Journal Biochemistry
Year 1994
Volume 33
Pages 7691-700
Authors Holmberg E, Olausson T, Hultman T, Rydstrom J, Ahmad S, Glavas NA, Bragg PD
Title Prediction and site-specific mutagenesis of residues in transmembrane alpha-helices of proton-pumping nicotinamide nucleotide transhydrogenases from Escherichia coli and bovine heart mitochondria.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9804876
Journal Biochim Biophys Acta
Year 1998
Volume 1409
Pages 25-38
Authors Gupta S, Quirk PG, Venning JD, Slade J, Bizouarn T, Grimley RL, Cotton NP, Jackson JB
Title Mutation of amino acid residues in the mobile loop region of the NAD(H)-binding domain of proton-translocating transhydrogenase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 10393090
Journal Biochem J
Year 1999
Volume 341
Pages 329-37
Authors Venning JD, Jackson JB
Title A shift in the equilibrium constant at the catalytic site of proton-translocating transhydrogenase: significance for a 'binding-change' mechanism.
Related PDB
Related UniProtKB
[4]
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
[5]
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
[6]
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
[7]
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
[8]
Resource
Comments NMR Structure
Medline ID
PubMed ID 11004437
Journal Biochim Biophys Acta
Year 2000
Volume 1459
Pages 248-57
Authors Jeeves M, Smith KJ, Quirk PG, Cotton NP, Jackson JB
Title Solution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from Rhodospirillum rubrum.
Related PDB 1e3t
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10747934
Journal J Biol Chem
Year 2000
Volume 275
Pages 19490-7
Authors Venning JD, Peake SJ, Quirk PG, Jackson JB
Title Stopped-flow reaction kinetics of recombinant components of proton-translocating transhydrogenase with physiological nucleotides.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10997900
Journal Structure Fold Des
Year 2000
Volume 8
Pages 809-15
Authors Buckley PA, Baz Jackson J, Schneider T, White SA, Rice DW, Baker PJ
Title Protein-protein recognition, hydride transfer and proton pumping in the transhydrogenase complex.
Related PDB 1f8g
Related UniProtKB
[11]
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
[12]
Resource
Comments
Medline ID
PubMed ID 11577115
Journal J Biol Chem
Year 2001
Volume 276
Pages 44757-61
Authors Pinheiro TJ, Venning JD, Jackson JB
Title Fast hydride transfer in proton-translocating transhydrogenase revealed in a rapid mixing continuous flow device.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11399770
Journal J Biol Chem
Year 2001
Volume 276
Pages 30678-85
Authors Venning JD, Rodrigues DJ, Weston CJ, Cotton NP, Quirk PG, Errington N, Finet S, White SA, Jackson JB
Title The heterotrimer of the membrane-peripheral components of transhydrogenase and the alternating-site mechanism of proton translocation.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11250201
Journal Structure (Camb)
Year 2001
Volume 9
Pages 165-76
Authors Cotton NP, White SA, Peake SJ, McSweeney S, Jackson JB
Title The crystal structure of an asymmetric complex of the two nucleotide binding components of proton-translocating transhydrogenase.
Related PDB 1hzz
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 12206884
Journal Biochim Biophys Acta
Year 2002
Volume 1555
Pages 8-13
Authors Rodrigues DJ, Jackson JB
Title A conformational change in the isolated NADP(H)-binding component (dIII) of transhydrogenase induced by low pH: a reflection of events during proton translocation by the complete enzyme?
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12379117
Journal Biochemistry
Year 2002
Volume 41
Pages 12745-54
Authors Prasad GS, Wahlberg M, Sridhar V, Sundaresan V, Yamaguchi M, Hatefi Y, Stout CD
Title Crystal structures of transhydrogenase domain I with and without bound NADH.
Related PDB 1l7d 1l7e
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 14567675
Journal Biochemistry
Year 2003
Volume 42
Pages 12143-53
Authors Sundaresan V, Yamaguchi M, Chartron J, Stout CD
Title Conformational change in the NADP(H) binding domain of transhydrogenase defines four states.
Related PDB 1pno 1pnq
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 12564924
Journal Biochemistry
Year 2003
Volume 42
Pages 1217-26
Authors van Boxel GI, Quirk PG, Cotton NP, White SA, Jackson JB
Title Glutamine 132 in the NAD(H)-binding component of proton-translocating transhydrogenase tethers the nucleotides before hydride transfer.
Related PDB 1nm5
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 12765762
Journal Biochim Biophys Acta
Year 2003
Volume 1604
Pages 55-9
Authors Pedersen A, Karlsson J, Althage M, Rydstrom J
Title Properties of the apo-form of the NADP(H)-binding domain III of proton-pumping Escherichia coli transhydrogenase: implications for the reaction mechanism of the intact enzyme.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 12972415
Journal J Biol Chem
Year 2003
Volume 278
Pages 47578-84
Authors Broos J, Gabellieri E, van Boxel GI, Jackson JB, Strambini GB
Title Tryptophan phosphorescence spectroscopy reveals that a domain in the NAD(H)-binding component (dI) of transhydrogenase from Rhodospirillum rubrum has an extremely rigid and conformationally homogeneous protein core.
Related PDB
Related UniProtKB
[21]
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
[22]
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 two alpha chains and a beta chain. Alpha-1 chain is homologous to the domain I (N-terminal matrix domain) of NAD(P)+ transhydrogenase from mammalian mitochondrial membrane (Swissprot P11024, Q13423; M00162 of EzCatDB), whilst beta chain is thomologous to the domain III (C-terminal matrix domain) of the counterpart enzyme. Although the tertiary structures of these chains have been solved, the structure of the remainder, alpha-2 subunit, which is a membrane-bound protein, has not been determined yet.

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