1pm9
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The side chains of His30 and Tyr166 from adjacent subunits in the | + | The side chains of His30 and Tyr166 from adjacent subunits in the homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the dimer interface and participate in a hydrogen-bonded network that extends to the active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant showed 10-fold decreases in steady-state constants for catalysis measured by pulse radiolysis. The observation of no additional effect upon the second mutation is an example of cooperatively interacting residues. A similar effect was observed in the thermal stability of these enzymes; the double mutant did not reduce the major unfolding transition to an extent greater than either single mutant. The crystal structures of these site-specific mutants each have unique conformational changes, but each has lost the hydrogen bond across the dimer interface, which results in a decrease in catalysis. These same mutations caused an enhancement of the dissociation of the product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex. This would have a selective advantage in blocking a cellular overproduction of toxic H2O2. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Superoxide dismutase]] | [[Category: Superoxide dismutase]] | ||
[[Category: Fan, L.]] | [[Category: Fan, L.]] | ||
| - | [[Category: Tainer, J | + | [[Category: Tainer, J A.]] |
[[Category: MN3]] | [[Category: MN3]] | ||
[[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 Thu Feb 21 14:30:14 2008'' |
Revision as of 12:30, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN MNSOD H30N, Y166F MUTANT
Overview
The side chains of His30 and Tyr166 from adjacent subunits in the homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the dimer interface and participate in a hydrogen-bonded network that extends to the active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant showed 10-fold decreases in steady-state constants for catalysis measured by pulse radiolysis. The observation of no additional effect upon the second mutation is an example of cooperatively interacting residues. A similar effect was observed in the thermal stability of these enzymes; the double mutant did not reduce the major unfolding transition to an extent greater than either single mutant. The crystal structures of these site-specific mutants each have unique conformational changes, but each has lost the hydrogen bond across the dimer interface, which results in a decrease in catalysis. These same mutations caused an enhancement of the dissociation of the product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex. This would have a selective advantage in blocking a cellular overproduction of toxic H2O2.
About this Structure
1PM9 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Superoxide dismutase, with EC number 1.15.1.1 Full crystallographic information is available from OCA.
Reference
Amino acid substitution at the dimeric interface of human manganese superoxide dismutase., Hearn AS, Fan L, Lepock JR, Luba JP, Greenleaf WB, Cabelli DE, Tainer JA, Nick HS, Silverman DN, J Biol Chem. 2004 Feb 13;279(7):5861-6. Epub 2003 Nov 24. PMID:14638684
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