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1ja8

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Revision as of 09:18, 17 January 2018

Kinetic Analysis of Product Inhibition in Human Manganese Superoxide Dismutase

Structural highlights

1ja8 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:	1abm, 1em1, 1ap5, 1ap6
Activity:	Superoxide dismutase, with EC number 1.15.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SODM_HUMAN] Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:612634]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.

Function

[SODM_HUMAN] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.^[1]

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

Manganese superoxide dismutase (MnSOD) cycles between the Mn(II) and Mn(III) states during the catalyzed disproportionation of O(2)(*-), a catalysis that is limited at micromolar levels of superoxide by a peroxide-inhibited complex with the metal. We have investigated the role in catalysis and inhibition of the conserved residue Trp161 which forms a hydrophobic side of the active site cavity of MnSOD. Crystal structures of mutants of human MnSOD in which Trp161 was replaced with Ala or Phe showed significant conformational changes on adjacent residues near the active site, particularly Gln143 and Tyr34 which in wild-type MnSOD participate in a hydrogen bond network believed to support proton transfer during catalysis. Using pulse radiolysis and observing the UV absorbance of superoxide, we have determined rate constants for the catalytic dismutation of superoxide. In addition, the rates of formation and dissociation of the product-inhibited complex of these mutants were determined by direct observation of the characteristic visible absorption of the oxidized and inhibited states. Catalysis by W161A and W161F MnSOD was associated with a decrease of at least 100-fold in the catalytic rate of reduction of superoxide, which then promotes a competing pathway leading to product inhibition. The structural changes caused by the mutations at position 161 led to small changes, at most a 6-fold decrease, in the rate constant for formation of the inhibited complex. Solvent hydrogen isotope effects support a mechanism in which formation of this complex, presumably the peroxide dianion bound to the manganese, involves no rate-contributing proton transfer; however, the dissociation of the complex requires proton transfer to generate HO(2)(-) or H2O2.

Kinetic analysis of product inhibition in human manganese superoxide dismutase.,Hearn AS, Stroupe ME, Cabelli DE, Lepock JR, Tainer JA, Nick HS, Silverman DN Biochemistry. 2001 Oct 9;40(40):12051-8. PMID:11580280^[2]

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

References

↑ MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999 Jun 1;366(1):82-8. PMID:10334867 doi:S0003-9861(99)91202-X
↑ Hearn AS, Stroupe ME, Cabelli DE, Lepock JR, Tainer JA, Nick HS, Silverman DN. Kinetic analysis of product inhibition in human manganese superoxide dismutase. Biochemistry. 2001 Oct 9;40(40):12051-8. PMID:11580280

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/1ja8"

@@ Line 1: / Line 1: @@
 ==Kinetic Analysis of Product Inhibition in Human Manganese Superoxide Dismutase==
 <StructureSection load='1ja8' size='340' side='right' caption='[[1ja8]], [[Resolution|resolution]] 2.12&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1abm|1abm]], [[1em1|1em1]], [[1ap5|1ap5]], [[1ap6|1ap6]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=1ja8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ja8 OCA], [http://pdbe.org/1ja8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ja8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ja8 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=1ja8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ja8 OCA], [http://pdbe.org/1ja8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ja8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ja8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ja8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ja/1ja8_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ja/1ja8_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 1ja8" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Superoxide Dismutase|Superoxide Dismutase]]
 == References ==
 <references/>

1ja8

From Proteopedia

Revision as of 09:18, 17 January 2018

Kinetic Analysis of Product Inhibition in Human Manganese Superoxide Dismutase

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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