1pt9
Crystal Structure Analysis of the DIII Component of Transhydrogenase with a Thio-Nicotinamide Nucleotide AnalogueCrystal Structure Analysis of the DIII Component of Transhydrogenase with a Thio-Nicotinamide Nucleotide Analogue
Template:ABSTRACT PUBMED 12791694
DiseaseDisease
[NNTM_HUMAN] Defects in NNT are the cause of glucocorticoid deficiency type 4 (GCCD4) [MIM:614736]. A rare, potentially lethal, autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.[1]
FunctionFunction
[NNTM_HUMAN] The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane. May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland.[2]
About this StructureAbout this Structure
1pt9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Singh A, Venning JD, Quirk PG, van Boxel GI, Rodrigues DJ, White SA, Jackson JB. 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. 2003 Aug 29;278(35):33208-16. Epub 2003 Jun 5. PMID:12791694 doi:10.1074/jbc.M303061200
- ↑ Bhakta T, Whitehead SJ, Snaith JS, Dafforn TR, Wilkie J, Rajesh S, White SA, Jackson JB. Structures of the dI2dIII1 complex of proton-translocating transhydrogenase with bound, inactive analogues of NADH and NADPH reveal active site geometries. Biochemistry. 2007 Mar 20;46(11):3304-18. Epub 2007 Feb 27. PMID:17323922 doi:10.1021/bi061843r
- ↑ Meimaridou E, Kowalczyk J, Guasti L, Hughes CR, Wagner F, Frommolt P, Nurnberg P, Mann NP, Banerjee R, Saka HN, Chapple JP, King PJ, Clark AJ, Metherell LA. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat Genet. 2012 May 27;44(7):740-2. doi: 10.1038/ng.2299. PMID:22634753 doi:10.1038/ng.2299
- ↑ Meimaridou E, Kowalczyk J, Guasti L, Hughes CR, Wagner F, Frommolt P, Nurnberg P, Mann NP, Banerjee R, Saka HN, Chapple JP, King PJ, Clark AJ, Metherell LA. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat Genet. 2012 May 27;44(7):740-2. doi: 10.1038/ng.2299. PMID:22634753 doi:10.1038/ng.2299