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1pt9

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Revision as of 10:01, 27 November 2019

Crystal Structure Analysis of the DIII Component of Transhydrogenase with a Thio-Nicotinamide Nucleotide Analogue

Structural highlights

1pt9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1ptj
Activity:	NAD(P)(+) transhydrogenase (Re/Si-specific), with EC number 1.6.1.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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]

Function

[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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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.,Singh A, Venning JD, Quirk PG, van Boxel GI, Rodrigues DJ, White SA, Jackson JB J Biol Chem. 2003 Aug 29;278(35):33208-16. Epub 2003 Jun 5. PMID:12791694^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pt9"

@@ Line 1: / Line 1: @@
 ==Crystal Structure Analysis of the DIII Component of Transhydrogenase with a Thio-Nicotinamide Nucleotide Analogue==
-<StructureSection load='1pt9' size='340' side='right' caption='[[1pt9]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
+<StructureSection load='1pt9' size='340' side='right'caption='[[1pt9]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1pt9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PT9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PT9 FirstGlance]. <br>
@@ Line 32: / Line 32: @@
 </div>
 <div class="pdbe-citations 1pt9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[NAD(P) transhydrogenase 3D structures|NAD(P) transhydrogenase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Boxel, G I.van]]
 [[Category: Jackson, J B]]

1pt9

From Proteopedia

Revision as of 10:01, 27 November 2019

Crystal Structure Analysis of the DIII Component of Transhydrogenase with a Thio-Nicotinamide Nucleotide Analogue

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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