1D4O

CRYSTAL STRUCTURE OF TRANSHYDROGENASE DOMAIN III AT 1.2 ANGSTROMS RESOLUTION

Summary for 1D4O

• Entry DOI: 10.2210/pdb1d4o/pdb
• Descriptor: NADP(H) TRANSHYDROGENASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: nucleotide-binding fold, protein-nadp(h) complex, inverted binding of nadp(h), oxidoreductase
• Biological source: Bos taurus (cattle)
• Cellular location: Mitochondrion inner membrane ; Multi-pass membrane protein ; Matrix side : P11024
• Total number of polymer chains: 1
• Total formula weight: 20761.47

Authors

Prasad, G.S.,Sridhar, V.,Yamaguchi, M.,Hatefi, Y.,Stout, C.D. (deposition date: 1999-10-04, release date: 2000-01-20, Last modification date: 2024-02-07)

Primary citation

Prasad, G.S.,Sridhar, V.,Yamaguchi, M.,Hatefi, Y.,Stout, C.D.
Crystal structure of transhydrogenase domain III at 1.2 A resolution.
Nat.Struct.Biol., 6:1126-1131, 1999

PubMed Abstract: The nicotinamide nucleotide transhydrogenases (TH) of mitochondria and bacteria are membrane-intercalated proton pumps that transduce substrate binding energy and protonmotive force via protein conformational changes. In mitochondria, TH utilizes protonmotive force to promote direct hydride ion transfer from NADH to NADP, which are bound at the distinct extramembranous domains I and III, respectively. Domain II is the membrane-intercalated domain and contains the enzyme's proton channel. This paper describes the crystal structure of the NADP(H) binding domain III of bovine TH at 1.2 A resolution. The structure reveals that NADP is bound in a manner inverted from that previously observed for nucleotide binding folds. The non-classical binding mode exposes the NADP(H) nicotinamide ring for direct contact with NAD(H) in domain I, in accord with biochemical data. The surface of domain III surrounding the exposed nicotinamide is comprised of conserved residues presumed to form the interface with domain I during hydride ion transfer. Further, an adjacent region contains a number of acidic residues, forming a surface with negative electrostatic potential which may interact with extramembranous loops of domain II. Together, the distinctive surface features allow mechanistic considerations regarding the NADP(H)-promoted conformation changes that are involved in the interactions of domain III with domains I and II for hydride ion transfer and proton translocation.

PubMed: 10581554
DOI: 10.1038/70067

Experimental method

X-RAY DIFFRACTION (1.21 Å)