5hbi: Difference between revisions
New page: left|200px<br /> <applet load="5hbi" size="450" color="white" frame="true" align="right" spinBox="true" caption="5hbi, resolution 1.6Å" /> '''SCAPHARCA DIMERIC HE... |
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[[Image:5hbi.gif|left|200px]]<br /> | [[Image:5hbi.gif|left|200px]]<br /><applet load="5hbi" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="5hbi, resolution 1.6Å" /> | caption="5hbi, resolution 1.6Å" /> | ||
'''SCAPHARCA DIMERIC HEMOGLOBIN, MUTANT T72I, CO-LIGANDED FORM'''<br /> | '''SCAPHARCA DIMERIC HEMOGLOBIN, MUTANT T72I, CO-LIGANDED FORM'''<br /> | ||
==Overview== | ==Overview== | ||
A cluster of interface ordered water molecules has been proposed to act as | A cluster of interface ordered water molecules has been proposed to act as a key mediator of intersubunit communication in the homodimeric hemoglobin of Scapharca inaequivalvis. Mutations of Thr72 to Val and Ile, which lack the hydroxyl group to hydrogen bond the deoxy interface water molecules, result in sharply altered functional properties. We have determined the high resolution (1.6-1. 8 A) crystal structures of these two mutants in both the deoxygenated and CO-liganded states. These structures show minimal protein structural changes relative to the same native derivatives, despite greater than 40-fold increases in oxygen affinity. In the deoxy state of both mutants two water molecules at the periphery of the water cluster are lost, and the remaining cluster water molecules are destabilized. The CO-liganded structures show key differences between the two mutants including a more optimal interface packing involving Ile72 that acts to stabilize its high affinity (R) state. This additional stabilization allows rationalization of its lowered cooperativity within the context of a two-state model. These studies support a key role of ordered water in cooperative functioning and illustrate how subtle structural alterations can result in significantly altered functional properties in an allosteric molecule. | ||
==About this Structure== | ==About this Structure== | ||
5HBI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Scapharca_inaequivalvis Scapharca inaequivalvis] with HEM and CMO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 5HBI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Scapharca_inaequivalvis Scapharca inaequivalvis] with <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=CMO:'>CMO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HBI OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Scapharca inaequivalvis]] | [[Category: Scapharca inaequivalvis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Junior, W | [[Category: Junior, W E.Royer.]] | ||
[[Category: CMO]] | [[Category: CMO]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
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[[Category: respiratory protein]] | [[Category: respiratory protein]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:15:22 2008'' | ||
Revision as of 20:15, 21 February 2008
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SCAPHARCA DIMERIC HEMOGLOBIN, MUTANT T72I, CO-LIGANDED FORM
OverviewOverview
A cluster of interface ordered water molecules has been proposed to act as a key mediator of intersubunit communication in the homodimeric hemoglobin of Scapharca inaequivalvis. Mutations of Thr72 to Val and Ile, which lack the hydroxyl group to hydrogen bond the deoxy interface water molecules, result in sharply altered functional properties. We have determined the high resolution (1.6-1. 8 A) crystal structures of these two mutants in both the deoxygenated and CO-liganded states. These structures show minimal protein structural changes relative to the same native derivatives, despite greater than 40-fold increases in oxygen affinity. In the deoxy state of both mutants two water molecules at the periphery of the water cluster are lost, and the remaining cluster water molecules are destabilized. The CO-liganded structures show key differences between the two mutants including a more optimal interface packing involving Ile72 that acts to stabilize its high affinity (R) state. This additional stabilization allows rationalization of its lowered cooperativity within the context of a two-state model. These studies support a key role of ordered water in cooperative functioning and illustrate how subtle structural alterations can result in significantly altered functional properties in an allosteric molecule.
About this StructureAbout this Structure
5HBI is a Single protein structure of sequence from Scapharca inaequivalvis with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Mutational destabilization of the critical interface water cluster in Scapharca dimeric hemoglobin: structural basis for altered allosteric activity., Pardanani A, Gambacurta A, Ascoli F, Royer WE Jr, J Mol Biol. 1998 Dec 4;284(3):729-39. PMID:9826511
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