5hbi
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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 HEM and CMO 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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