2gds
From Proteopedia
(New page: 200px<br /> <applet load="2gds" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gds, resolution 2.30Å" /> '''Interrupting the Hy...) |
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| - | [[Image:2gds.gif|left|200px]]<br /> | + | [[Image:2gds.gif|left|200px]]<br /><applet load="2gds" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2gds" size=" | + | |
caption="2gds, resolution 2.30Å" /> | caption="2gds, resolution 2.30Å" /> | ||
'''Interrupting the Hydrogen Bonding Network at the Active Site of Human Manganese Superoxide Dismutase'''<br /> | '''Interrupting the Hydrogen Bonding Network at the Active Site of Human Manganese Superoxide Dismutase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Histidine 30 in human manganese superoxide dismutase (MnSOD) is located at | + | Histidine 30 in human manganese superoxide dismutase (MnSOD) is located at a site partially exposed to solvent with its side chain participating in a hydrogen-bonded network that includes the active-site residues Tyr(166) and Tyr(34) and extends to the manganese-bound solvent molecule. We have replaced His(30) with a series of amino acids and Tyr(166) with Phe in human MnSOD. The crystal structure of the mutant of MnSOD containing Asn(30) superimposed closely with the wild type, but the side chain of Asn(30) did not participate in the hydrogen-bonded network in the active site. The catalytic activity of a number of mutants with replacements at position 30 and for the mutant containing Phe(166) showed a 10-40-fold decrease in k(cat). This is the same magnitude of decrease in k(cat) obtained with the replacement of Tyr(34) by Phe, suggesting that interrupting the hydrogen-bonded active-site network at any of the sites of these three participants (His(30), Tyr(34), and Tyr(166)) leads to an equivalent decrease in k(cat) and probably less efficient proton transfer to product peroxide. The specific geometry of His(30) on the hydrogen bond network is essential for stability since the disparate mutations H30S, H30A, and H30Q reduce T(m) by similar amounts (10-16 degrees C) compared with wild type. |
==About this Structure== | ==About this Structure== | ||
| - | 2GDS 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 MN as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 2GDS 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=MN:'>MN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=2GDS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Superoxide dismutase]] | [[Category: Superoxide dismutase]] | ||
| - | [[Category: Perry, J | + | [[Category: Perry, J J.]] |
[[Category: MN]] | [[Category: MN]] | ||
[[Category: h30n mutation]] | [[Category: h30n mutation]] | ||
[[Category: human manganese superoxide dismutase]] | [[Category: human manganese superoxide dismutase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:30:43 2008'' |
Revision as of 15:30, 21 February 2008
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Interrupting the Hydrogen Bonding Network at the Active Site of Human Manganese Superoxide Dismutase
Overview
Histidine 30 in human manganese superoxide dismutase (MnSOD) is located at a site partially exposed to solvent with its side chain participating in a hydrogen-bonded network that includes the active-site residues Tyr(166) and Tyr(34) and extends to the manganese-bound solvent molecule. We have replaced His(30) with a series of amino acids and Tyr(166) with Phe in human MnSOD. The crystal structure of the mutant of MnSOD containing Asn(30) superimposed closely with the wild type, but the side chain of Asn(30) did not participate in the hydrogen-bonded network in the active site. The catalytic activity of a number of mutants with replacements at position 30 and for the mutant containing Phe(166) showed a 10-40-fold decrease in k(cat). This is the same magnitude of decrease in k(cat) obtained with the replacement of Tyr(34) by Phe, suggesting that interrupting the hydrogen-bonded active-site network at any of the sites of these three participants (His(30), Tyr(34), and Tyr(166)) leads to an equivalent decrease in k(cat) and probably less efficient proton transfer to product peroxide. The specific geometry of His(30) on the hydrogen bond network is essential for stability since the disparate mutations H30S, H30A, and H30Q reduce T(m) by similar amounts (10-16 degrees C) compared with wild type.
About this Structure
2GDS 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
Interrupting the hydrogen bond network at the active site of human manganese superoxide dismutase., Ramilo CA, Leveque V, Guan Y, Lepock JR, Tainer JA, Nick HS, Silverman DN, J Biol Chem. 1999 Sep 24;274(39):27711-6. PMID:10488113
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