2hrn

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Revision as of 06:32, 27 June 2018

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Solution Structure of Cu(I) P174L-HSco1

Structural highlights

2hrn is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2gqk, 2gql, 2gqm, 2gt6, 2gt5, 2gvp, 2hrf
Gene:	SCO1, SCOD1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Warning: this is a large structure, and loading might take a long time or not happen at all.

Disease

[SCO1_HUMAN] Defects in SCO1 are a cause of mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]; also known as cytochrome c oxidase deficiency. A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation. A subset of patients manifest Leigh syndrome.^[1] ^[2]

Function

[SCO1_HUMAN] Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX.^[3] ^[4] ^[5]

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

The pathogenic mutant (P174L) of human Sco1 produces respiratory chain deficiency associated with cytochrome c oxidase (CcO) assembly defects. The solution structure of the mutant in its Cu(I) form shows that Leu-174 prevents the formation of a well packed hydrophobic region around the metal-binding site and causes a reduction of the affinity of copper(I) for the protein. K(D) values for Cu(I)WT-HSco1 and Cu(I)P174L-HSco1 are approximately 10(-17) and approximately 10(-13), respectively. The reduction potentials of the two apo proteins are similar, but slower reduction/oxidation rates are found for the mutant with respect to the WT. The mitochondrial metallochaperone in the partially oxidized Cu(1)(I)Cox17(2S-S) form, at variance with the fully reduced Cu(4)(I)Cox17, interacts transiently with both WT-HSco1 and the mutant, forming the Cox17/Cu(I)/HSco1 complex, but copper is efficiently transferred only in the case of WT protein. Cu(1)(I)Cox17(2S-S) indeed has an affinity for copper(I) (K(D) approximately 10(-15)) higher than that of the P174L-HSco1 mutant but lower than that of WT-HSco1. We propose that HSco1 mutation, altering the structure around the metal-binding site, affects both copper(I) binding and redox properties of the protein, thus impairing the efficiency of copper transfer to CcO. The pathogenic mutation therefore could (i) lessen the Sco1 affinity for copper(I) and hence copper supply for CcO or (ii) decrease the efficiency of reduction of CcO thiols involved in copper binding, or both effects could be produced by the mutation.

Human Sco1 functional studies and pathological implications of the P174L mutant.,Banci L, Bertini I, Ciofi-Baffoni S, Leontari I, Martinelli M, Palumaa P, Sillard R, Wang S Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):15-20. Epub 2006 Dec 20. PMID:17182746^[6]

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

References

↑ Leary SC, Cobine PA, Kaufman BA, Guercin GH, Mattman A, Palaty J, Lockitch G, Winge DR, Rustin P, Horvath R, Shoubridge EA. The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. Cell Metab. 2007 Jan;5(1):9-20. PMID:17189203 doi:10.1016/j.cmet.2006.12.001
↑ Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rotig A. Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. Am J Hum Genet. 2000 Nov;67(5):1104-9. Epub 2000 Sep 28. PMID:11013136 doi:10.1016/S0002-9297(07)62940-1
↑ Leary SC, Cobine PA, Kaufman BA, Guercin GH, Mattman A, Palaty J, Lockitch G, Winge DR, Rustin P, Horvath R, Shoubridge EA. The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. Cell Metab. 2007 Jan;5(1):9-20. PMID:17189203 doi:10.1016/j.cmet.2006.12.001
↑ Williams JC, Sue C, Banting GS, Yang H, Glerum DM, Hendrickson WA, Schon EA. Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein. J Biol Chem. 2005 Apr 15;280(15):15202-11. Epub 2005 Jan 19. PMID:15659396 doi:10.1074/jbc.M410705200
↑ Banci L, Bertini I, Calderone V, Ciofi-Baffoni S, Mangani S, Martinelli M, Palumaa P, Wang S. A hint for the function of human Sco1 from different structures. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8595-600. Epub 2006 May 30. PMID:16735468
↑ Banci L, Bertini I, Ciofi-Baffoni S, Leontari I, Martinelli M, Palumaa P, Sillard R, Wang S. Human Sco1 functional studies and pathological implications of the P174L mutant. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):15-20. Epub 2006 Dec 20. PMID:17182746

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hrn"

@@ Line 1: / Line 1: @@
+{{Large structure}}
 ==Solution Structure of Cu(I) P174L-HSco1==
 <StructureSection load='2hrn' size='340' side='right' caption='[[2hrn]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gqk|2gqk]], [[2gql|2gql]], [[2gqm|2gqm]], [[2gt6|2gt6]], [[2gt5|2gt5]], [[2gvp|2gvp]], [[2hrf|2hrf]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCO1, SCOD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2hrn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hrn OCA], [http://pdbe.org/2hrn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hrn RCSB], [http://www.ebi.ac.uk/pdbsum/2hrn 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=2hrn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hrn OCA], [http://pdbe.org/2hrn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hrn RCSB], [http://www.ebi.ac.uk/pdbsum/2hrn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hrn ProSAT]</span></td></tr>
 </table>
 {{Large structure}}
@@ Line 17: / Line 18: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/2hrn_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/2hrn_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2hrn

From Proteopedia

Revision as of 06:32, 27 June 2018

Solution Structure of Cu(I) P174L-HSco1

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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