PDBsum entry: 1ptj

Oxidoreductase

PDB id: 1ptj

Contents

Protein chains

362 a.a. *

174 a.a. *

Ligands

SND

GOL ×3

NAP

Waters ×146

* Residue conservation analysis

PDB id:

1ptj

Name:

Oxidoreductase

Title:

Crystal structure analysis of the di and diii complex of transhydrogenase with a thio-nicotinamide nucleotide analog

Structure:

NAD(p) transhydrogenase subunit alpha part 1. Chain: a, b. Synonym: pyridine nucleotide transhydrogenase subunit alpha nicotinamide nucleotide transhydrogenase subunit alpha 1, p translocating transhydrogenase component 1, di. NAD(p) transhydrogenase subunit beta. Chain: c. Fragment: residues 291-464. Synonym: pyridine nucleotide transhydrogenase subunit beta,

Source:

Rhodospirillum rubrum. Organism_taxid: 1085. Organism_taxid: 1085

Biol. unit:

Trimer (from PQS)

Resolution:

2.61Å R-factor: 0.234 R-free: 0.287

Authors:

A.Singh,J.D.Venning,P.G.Quirk,G.I.Van Boxel,D.J.Rodrigues,S. J.B.Jackson

Key ref:

A.Singh et al. (2003). 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. J Biol Chem, 278, 33208-33216. PubMed id: 12791694 DOI: 10.1074/jbc.M303061200

Date:

23-Jun-03 Release date: 07-Oct-03

Protein chains

P0C186  (PNTAA_RHORU) -  NAD(P) transhydrogenase subunit alpha part 1

Seq: 384 a.a.

Struc: 362 a.a.

Protein chain

P0C188  (PNTB_RHORU) -  NAD(P) transhydrogenase subunit beta

Seq: 464 a.a.

Struc: 174 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.1.6.1.2 - NAD(P)(+) transhydrogenase (AB-specific).
• Reaction: NADPH + NAD⁺ = NADP⁺ + NADH

NADPH (Bound ligand (Het Group name = NAP) corresponds exactly) + NAD(+) = NADP(+) + NADH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: integral to membrane (1 term)
• Biological process: oxidation-reduction process (1 term)
• Biochemical function: oxidoreductase activity (3 terms)

reference

DOI no: 10.1074/jbc.M303061200

J Biol Chem 278:33208-33216 (2003)

PubMed id: 12791694

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.

A.Singh, J.D.Venning, P.G.Quirk, G.I.van Boxel, D.J.Rodrigues, S.A.White, J.B.Jackson.

ABSTRACT

Transhydrogenase couples the reduction of NADP+ by NADH to inward proton translocation across mitochondrial and bacterial membranes. The coupling reactions occur within the protein by long distance conformational changes. In intact transhydrogenase and in complexes formed from the isolated, nucleotide-binding components, thio-NADP(H) is a good analogue for NADP(H), but thio-NAD(H) is a poor analogue for NAD(H). Crystal structures of the nucleotide-binding components show that the twists of the 3-carbothiamide groups of thio-NADP+ and of thio-NAD+ (relative to the planes of the pyridine rings), which are defined by the dihedral, Xam, are altered relative to the twists of the 3-carboxamide groups of the physiological nucleotides. The finding that thio-NADP+ is a good substrate despite an increased Xam value shows that approach of the NADH prior to hydride transfer is not obstructed by the S atom in the analogue. That thio-NAD(H) is a poor substrate appears to be the result of failure in the conformational change that establishes the ground state for hydride transfer. This might be a consequence of restricted rotation of the 3-carbothiamide group during the conformational change.

Selected figure(s)

Figure 6.
FIG. 6. NADP+ (left) and thio-NADP+ (right) in the nucleotide-binding site of isolated human dIII. The nucleotide is shown with thick bonds, and some of the polypeptide backbone and selected side chains with are shown with thin bonds. The dotted orange line shows an hydrogen bond between the carboxamide (or carbothiamide) group and the protein.

Figure 7.
FIG. 7. The nicotinamide ring (of NAD^+, left) and the thio-nicotinamide ring (of thio-NAD^+, right) in the dI(A) polypeptide of the R. rubrum dI[2]dIII[1] complex. Van der Waals' surfaces of amino acid residues are shown in red, and those of nucleotides are in blue. The black dotted line shows a hydrogen bond between Ile^128O and the carboxamide group of NAD^+ (3.05 Å). An equivalent hydrogen bond to the carbothiamide group of thio-NAD^+ is precluded by the increased interatomic distance (3.3 Å). The arrows in the figure are only for labeling purposes.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 33208-33216) copyright 2003.

Figures were selected by the author.