1u31

From Proteopedia

(Difference between revisions)

Revision as of 08:22, 21 March 2018

recombinant human heart transhydrogenase dIII bound with NADPH

Structural highlights

1u31 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1djl, 1pt9, 1u28, 1u2d, 1u2g
Gene:	NNT (HUMAN)
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 redox (hydride-transfer) reaction between NAD(H) and NADP(H) to proton translocation across a membrane. The redox reaction is catalyzed at the interface between two components (dI and dIII) which protrude from the membrane. A complex formed from recombinant dI and dIII (the dI(2)dIII(1) complex) from Rhodospirillum rubrum transhydrogenase catalyzes fast single-turnover hydride transfer between bound nucleotides. In this report we describe three new crystal structures of the dI(2)dIII(1) complex in different nucleotide-bound forms. The structures reveal an asymmetry in nucleotide binding that complements results from solution studies and supports the notion that intact transhydrogenase functions by an alternating site mechanism. In one structure, the redox site is occupied by NADH (on dI) and NADPH (on dIII). The dihydronicotinamide rings take up positions which may approximate to the ground state for hydride transfer: the redox-active C4(N) atoms are separated by only 3.6 A, and the perceived reaction stereochemistry matches that observed experimentally. The NADH conformation is different in the two dI polypeptides of this form of the dI(2)dIII(1) complex. Comparisons between a number of X-ray structures show that a conformational change in the NADH is driven by relative movement of the two domains which comprise dI. It is suggested that an equivalent conformational change in the intact enzyme is important in gating the hydride-transfer reaction. The observed nucleotide conformational change in the dI(2)dIII(1) complex is accompanied by rearrangements in the orientation of local amino acid side chains which may be responsible for sealing the site from the solvent and polarizing hydride transfer.

Active-site conformational changes associated with hydride transfer in proton-translocating transhydrogenase.,Mather OC, Singh A, van Boxel GI, White SA, Jackson JB Biochemistry. 2004 Aug 31;43(34):10952-64. PMID:15323555^[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
↑ Mather OC, Singh A, van Boxel GI, White SA, Jackson JB. Active-site conformational changes associated with hydride transfer in proton-translocating transhydrogenase. Biochemistry. 2004 Aug 31;43(34):10952-64. PMID:15323555 doi:10.1021/bi0497594

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/1u31"

@@ Line 1: / Line 1: @@
 ==recombinant human heart transhydrogenase dIII bound with NADPH==
 <StructureSection load='1u31' size='340' side='right' caption='[[1u31]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NNT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(P)(+)_transhydrogenase_(Re/Si-specific) NAD(P)(+) transhydrogenase (Re/Si-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.1.2 1.6.1.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u31 OCA], [http://pdbe.org/1u31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u31 RCSB], [http://www.ebi.ac.uk/pdbsum/1u31 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u31 OCA], [http://pdbe.org/1u31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u31 RCSB], [http://www.ebi.ac.uk/pdbsum/1u31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u31 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u3/1u31_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u3/1u31_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1u31

From Proteopedia

Revision as of 08:22, 21 March 2018

recombinant human heart transhydrogenase dIII bound with NADPH

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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