1qnm
From Proteopedia
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|PDB= 1qnm |SIZE=350|CAPTION= <scene name='initialview01'>1qnm</scene>, resolution 2.3Å | |PDB= 1qnm |SIZE=350|CAPTION= <scene name='initialview01'>1qnm</scene>, resolution 2.3Å | ||
|SITE= <scene name='pdbsite=MNA:Catalytic+Site'>MNA</scene> | |SITE= <scene name='pdbsite=MNA:Catalytic+Site'>MNA</scene> | ||
| - | |LIGAND= <scene name='pdbligand=MN:MANGANESE (II) ION'>MN</scene> | + | |LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <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> |
|GENE= MUTATED RECOMBINANT HUMAN GENE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= MUTATED RECOMBINANT HUMAN GENE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qnm OCA], [http://www.ebi.ac.uk/pdbsum/1qnm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1qnm RCSB]</span> | ||
}} | }} | ||
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[[Category: Guan, Y.]] | [[Category: Guan, Y.]] | ||
[[Category: Tainer, J A.]] | [[Category: Tainer, J A.]] | ||
| - | [[Category: MN]] | ||
[[Category: hmnsod]] | [[Category: hmnsod]] | ||
[[Category: manganese superoxide dismutase]] | [[Category: manganese superoxide dismutase]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:16:25 2008'' |
Revision as of 20:16, 30 March 2008
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| , resolution 2.3Å | |||||||
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| Sites: | |||||||
| Ligands: | |||||||
| Gene: | MUTATED RECOMBINANT HUMAN GENE (Homo sapiens) | ||||||
| Activity: | Superoxide dismutase, with EC number 1.15.1.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN MANGANESE SUPEROXIDE DISMUTASE MUTANT Q143N
Overview
Structural and biochemical characterization of the nonliganding residue glutamine 143 near the manganese of human Mn superoxide dismutase (hMnSOD), a homotetramer of 22 kDa, reveals a functional role for this residue. In the wild-type protein, the side-chain amide group of Gln 143 is about 5 A from the metal and is hydrogen-bonded to Tyr 34, which is a second prominent side chain adjacent to the metal. We have prepared the site-specific mutant of hMnSOD with the conservative replacement of Gln 143 --> Asn (Q143N). The crystal structure of Q143N shows that the side-chain amide nitrogen of residue 143 is 1.7 A more distant from the manganese than in the wild-type enzyme. The Tyr 34 side-chain hydroxyl in Q143N is also moved to become 0.6 A more distant from the metal due to an additional water molecule. Differential scanning calorimetry showed that Q143N is slightly more stable than the wild-type enzyme with Tm for the main unfolding transition increased by 2 degrees C to 90.7 degrees C. Pulse radiolysis and stopped-flow spectrophotometry reveal that unlike wild-type hMnSOD, which is strongly inhibited by peroxide, Q143N MnSOD exhibits no product inhibition even at concentrations of O2. - in the millimolar range, and its catalysis follows Michaelis kinetics with no evidence of cooperativity. However, the overall catalytic activity of this mutant was decreased 2-3 orders of magnitude compared with the wild-type MnSOD, which can account for its lack of product inhibition. Q143N MnSOD lacked the visible absorption spectrum typical of wild-type Mn(III)SOD. Also, unlike the wild-type Mn(III)SOD, which is electron paramagnetic resonance (EPR) silent, Q143N MnSOD has a complex EPR spectrum with many resonances in the region below 2250 G. We conclude that the Gln 143 --> Asn mutation has increased the reduction potential of manganese to stabilize Mn(II), indicating that Gln 143 has a substantial role in maintaining a reduction potential favorable for the oxidation and reduction cycles in the catalytic disproportionation of superoxide. A solvent hydrogen isotope effect near 2 for kcat in catalysis by Q143N hMnSOD indicates rate-contributing proton transfers to form product hydroperoxide anion or hydrogen peroxide. The data demonstrate a prominent role for Gln 143 in maintaining the microenvironment of the manganese and in efficient catalysis of superoxide dismutation to oxygen and hydrogen peroxide.
About this Structure
1QNM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Probing the active site of human manganese superoxide dismutase: the role of glutamine 143., Hsieh Y, Guan Y, Tu C, Bratt PJ, Angerhofer A, Lepock JR, Hickey MJ, Tainer JA, Nick HS, Silverman DN, Biochemistry. 1998 Apr 7;37(14):4731-9. PMID:9537988
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