Sandbox Reserved 164: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
Student (talk | contribs)
students
33,923 edits
No edit summary
Student (talk | contribs)
students
33,923 edits
No edit summary
 
(12 intermediate revisions by the same user not shown)
Line 1: Line 1:
<!-- PLEASE DO NOT DELETE THIS TEMPLATE -->
bla bla <Structure load='2nmz' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><!-- PLEASE DO NOT DELETE THIS TEMPLATE -->
{{Sandbox_Reserved_Irma_Santoro_7}}
<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
<Structure load='3ECU' size='500' frame='true' align='right' caption='SOD 1 protein NMR' scene='Insert optional scene name here' />
<Structure load='3ECU' size='500' frame='true' align='right' caption='Crystal Structure of SOD 1 protein, PDB ID: 3ECU' scene='Insert optional scene name here' />


== Superoxide Dismutase 1 (SOD 1) ==
SOD1 is one of three oxidoreductase enzymes that is responsible for binding copper and zinc ions to highly reactive oxygen free radicals and transforming them into oxygen and hydrogen peroxide. <ref name="McCord">McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049-55. PMID:5389100</ref>  This occurs in a quick two step mechanism:


== Superoxide Dismutase 1 (SOD 1) ==
Cu(2+)SOD + O2− → Cu(+)SOD + O2
SOD1 is one of three oxidoreductase enzymes that is responsible for binding copper and zinc ions to highly reactive oxygen free radicals and transforming them into oxygen and hydrogen peroxide <ref name="McCord">McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049-55. PMID:5389100</ref>.  This protein is coded for by the SOD 1 gene located on chromosome 21 at position 21q22.1 from base pairs 33,031,934 to 33,041,243 <ref name="Sod1">SOD 1.  Genetics Home Reference.  U.S. National Library of Medicine; 2010</ref>.
 
Cu(+)SOD + O2− + 2H+ → Cu(2+)SOD + H2O2<ref name="Tainer">Tainer JA, Getzoff ED, Richardson JS, Richardson DC. Structure and mechanism of copper, zinc superoxide dismutase. Nature. 1983 Nov 17-23;306(5940):284-7. PMID:6316150</ref>.


This protein is coded for by the SOD 1 gene located on chromosome 21 at position 21q22.1 from base pairs 33,031,934 to 33,041,243. <ref name="Sod1">SOD 1.  Genetics Home Reference.  U.S. National Library of Medicine; 2010</ref>


== Structure ==
== Structure ==
The SOD 1 protein is a homodimer with an amino acid sequence length of 154.  SOD 1 has an 8-stranded "Greek key" beta-barrel shape with the active site located between the barrels.  ligands of the copper and zinc are six histidine and one aspartate side-chains; one histidine is shared between the two metals<ref name="Tainer">Tainer JA, Getzoff ED, Richardson JS, Richardson DC. Structure and mechanism of copper, zinc superoxide dismutase. Nature. 1983 Nov 17-23;306(5940):284-7. PMID:6316150</ref>.
The SOD 1 protein is a homodimer with an amino acid sequence length of 154.  SOD 1 has an 8-stranded "Greek key" beta-barrel shape with the active site located between the barrels.  The copper and zinc ligands are made up of six histidine side-chains and one aspartate side-chain with the metal ions connected with by a single histidine chain.<ref name="Tainer">Tainer JA, Getzoff ED, Richardson JS, Richardson DC. Structure and mechanism of copper, zinc superoxide dismutase. Nature. 1983 Nov 17-23;306(5940):284-7. PMID:6316150</ref> This first SOD structure was determined by Irwin Fridovich and Joe McCord in 1973 <ref name="McCord">McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049-55. PMID:5389100</ref><ref name="McCord2">McCord JM, Fridovich I. Superoxide dismutase: the first twenty years (1968-1988). Free Radic Biol Med. 1988;5(5-6):363-9. PMID:2855736</ref> with the SOD 1 "Greek key" structure visualized by Dr. Jane Richardson (see below).<ref name="Tainer">Tainer JA, Getzoff ED, Richardson JS, Richardson DC. Structure and mechanism of copper, zinc superoxide dismutase. Nature. 1983 Nov 17-23;306(5940):284-7. PMID:6316150</ref>
[[Image:601px-2SOD ribbon pastel.jpg|300px|left]]


== ALS ==
== ALS ==
Mutations to the SOD 1 protein have been linked to the development of familial amyotrophic lateral sclerosis (Lou Gehrig's Disease). <ref name="Al-Chalabi">Al-Chalabi A, Leigh PN (August 2000). "Recent advances in amyotrophic lateral sclerosis". Curr. Opin. Neurol. 13 (4): 397–405. PMID 10970056.</ref>  These mutations cause a conformational change that leads to motor neuron death through toxic radical build up, promotion of apoptosis, aggregate formation of misfolded proteins, or over stimulation of the cells.<ref name="Sod1">SOD 1.  Genetics Home Reference.  U.S. National Library of Medicine; 2010</ref> In the United States, one of the most common SOD 1 protein mutations is the A4V mutation, where a point mutation causes the alanine at the 4th amino acid position to change to a valine; <ref name="Rosen">Rosen DR, Bowling AC, Patterson D, Usdin TB, Sapp P, Mezey E, McKenna-Yasek D, O'Regan J, Rahmani Z, Ferrante RJ (June 1994). "A frequent ala 4 to val superoxide dismutase-1 mutation is associated with a rapidly progressive familial amyotrophic lateral sclerosis". Hum. Mol. Genet. 3 (6): 981–7. PMID 7951249</ref> however, over 100 different mutations have been found in association with the onset of ALS.




== References ==
== References ==
<references />  
<references />
 
 
2. McCord JM, Fridovich I. Superoxide dismutase: the first twenty years (1968-1988). Free Radic Biol Med. 1988;5(5-6):363-9. PMID:2855736
Retrieved from "https://proteopedia.org/Sandbox_Reserved_164"