2gbv: Difference between revisions

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-[[Image:2gbv.jpg|left|200px]]<br /><applet load="2gbv" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2gbv, resolution 2.000&Aring;" />
-'''C6A/C111A/C57A/C146A holo CuZn Superoxide dismutase'''<br />
-==Overview==
+==C6A/C111A/C57A/C146A holo CuZn Superoxide dismutase==
-The gain of neurotoxic function in amyotrophic lateral sclerosis (ALS) has, been linked to misfolding of the homodimeric enzyme Cu/Zn superoxide, dismutase (SOD). Here, we present the crystal structure of fully, cysteine-depleted human SOD (SOD(CallA)), representing a reduced, marginally stable intermediate on the folding pathway in vivo that has, also been implicated as neurotoxic precursor state. A hallmark of this, species is that it fails to dimerize and becomes trapped as a monomer in, the absence of the active-site metals. The crystallographic data show that, removal of the C57-C146 disulphide bond sets free the interface loop IV in, the apo protein, whereas the same loop remains unaffected in the holo, protein. Thus, the low dimerisation propensity of disulphide-reduced, apoSOD seems to be of entropic origin due to increased loop flexibility in, the monomeric state: in the disulphide-reduced holo protein this gain in, configurational entropy upon splitting of the dimer interface is reduced, by the metal coordination.
+<StructureSection load='2gbv' size='340' side='right'caption='[[2gbv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2gbv]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GBV FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gbv OCA], [https://pdbe.org/2gbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gbv RCSB], [https://www.ebi.ac.uk/pdbsum/2gbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gbv ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SODC_HUMAN SODC_HUMAN] Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:[https://omim.org/entry/105400 105400]. ALS1 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms.<ref>PMID:12963370</ref> <ref>PMID:19741096</ref> <ref>PMID:8528216</ref> <ref>PMID:8682505</ref> <ref>PMID:9541385</ref> <ref>PMID:12754496</ref> <ref>PMID:15056757</ref> <ref>PMID:18378676</ref> [:]<ref>PMID:8446170</ref> <ref>PMID:8351519</ref> <ref>PMID:8179602</ref> <ref>PMID:7980516</ref> <ref>PMID:8069312</ref> <ref>PMID:7951252</ref> <ref>PMID:7881433</ref> <ref>PMID:7836951</ref> <ref>PMID:7997024</ref> <ref>PMID:7870076</ref> <ref>PMID:7887412</ref> <ref>PMID:7795609</ref> <ref>PMID:7655468</ref> <ref>PMID:7655469</ref> <ref>PMID:7655471</ref> <ref>PMID:7700376</ref> <ref>PMID:7647793</ref> <ref>PMID:7501156</ref> <ref>PMID:7496169</ref> <ref>PMID:8938700</ref> <ref>PMID:8907321</ref> <ref>PMID:8990014</ref> <ref>PMID:9101297</ref> <ref>PMID:9455977</ref> <ref>PMID:10732812</ref> <ref>PMID:9131652</ref> <ref>PMID:10400992</ref> <ref>PMID:10430435</ref> <ref>PMID:11535232</ref> <ref>PMID:11369193</ref> <ref>PMID:12402272</ref> <ref>PMID:12145308</ref> <ref>PMID:14506936</ref> <ref>PMID:18552350</ref> <ref>PMID:18301754</ref> <ref>PMID:21247266</ref> <ref>PMID:21220647</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/SODC_HUMAN SODC_HUMAN] Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gb/2gbv_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gbv ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The gain of neurotoxic function in amyotrophic lateral sclerosis (ALS) has been linked to misfolding of the homodimeric enzyme Cu/Zn superoxide dismutase (SOD). Here, we present the crystal structure of fully cysteine-depleted human SOD (SOD(CallA)), representing a reduced, marginally stable intermediate on the folding pathway in vivo that has also been implicated as neurotoxic precursor state. A hallmark of this species is that it fails to dimerize and becomes trapped as a monomer in the absence of the active-site metals. The crystallographic data show that removal of the C57-C146 disulphide bond sets free the interface loop IV in the apo protein, whereas the same loop remains unaffected in the holo protein. Thus, the low dimerisation propensity of disulphide-reduced apoSOD seems to be of entropic origin due to increased loop flexibility in the monomeric state: in the disulphide-reduced holo protein this gain in configurational entropy upon splitting of the dimer interface is reduced by the metal coordination.
-==Disease==
+The coupling between disulphide status, metallation and dimer interface strength in Cu/Zn superoxide dismutase.,Hornberg A, Logan DT, Marklund SL, Oliveberg M J Mol Biol. 2007 Jan 12;365(2):333-42. Epub 2006 Sep 23. PMID:17070542<ref>PMID:17070542</ref>
-Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147450 147450]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-GBV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CU1:'>CU1</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Superoxide_dismutase Superoxide dismutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.15.1.1 1.15.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GBV OCA].
+</div>
+<div class="pdbe-citations 2gbv" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-The coupling between disulphide status, metallation and dimer interface strength in Cu/Zn superoxide dismutase., Hornberg A, Logan DT, Marklund SL, Oliveberg M, J Mol Biol. 2007 Jan 12;365(2):333-42. Epub 2006 Sep 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17070542 17070542]
+*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Superoxide dismutase]]
+[[Category: Hornberg A]]
-[[Category: Hornberg, A.]]
+[[Category: Logan DT]]
-[[Category: Logan, D.T.]]
+[[Category: Marklund SL]]
-[[Category: Marklund, S.L.]]
+[[Category: Oliveberg M]]
-[[Category: Oliveberg, M.]]
-[[Category: CU1]]
-[[Category: ZN]]
-[[Category: cystein-free]]
-[[Category: human cu/zn superoxide dismutase]]
-[[Category: oxidoreductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:27:48 2008''