1j7s

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{{STRUCTURE_1j7s| PDB=1j7s | SCENE= }}
{{STRUCTURE_1j7s| PDB=1j7s | SCENE= }}
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'''Crystal Structure of deoxy HbalphaYQ, a mutant of HbA'''
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===Crystal Structure of deoxy HbalphaYQ, a mutant of HbA===
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==Overview==
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The effect of mutagenesis on O(2), CO, and NO binding to mutants of human hemoglobin, designed to modify some features of the reactivity that hinder use of hemoglobin solutions as blood substitute, has been extensively investigated. The kinetics may be interpreted in the framework of the Monod-Wyman-Changeux two-state allosteric model, based on the high-resolution crystallographic structures of the mutants and taking into account the control of heme reactivity by the distal side mutations. The mutations involve residues at topological position B10 and E7, i.e., Leu (B10) to Tyr and His (E7) to Gln, on either the alpha chains alone (yielding the hybrid tetramer Hbalpha(YQ)), the beta chains alone (hybrid tetramer Hbbeta(YQ)), or both types of chains (Hb(YQ)). Our data indicate that the two mutations affect ligand diffusion into the pocket, leading to proteins with low affinity for O(2) and CO, and especially with reduced reactivity toward NO, a difficult goal to achieve. The observed kinetic heterogeneity between the alpha(YQ) and beta(YQ) chains in Hb(YQ) has been rationalized on the basis of the three-dimensional structure of the active site. Furthermore, we report for the first time an experiment of partial CO binding, selective for the beta chains, to high salt crystals of the mutant Hb(YQ) in the T-state; these crystallographic data may be interpreted as "snapshots" of the initial events possibly occurring on ligand binding to the T-allosteric state of this peculiar mutant Hb.
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{{ABSTRACT_PUBMED_11724557}}
==Disease==
==Disease==
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[[Category: Vallone, B.]]
[[Category: Vallone, B.]]
[[Category: Globin]]
[[Category: Globin]]
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Revision as of 11:36, 1 July 2008

Image:1j7s.png

Template:STRUCTURE 1j7s

Contents

Crystal Structure of deoxy HbalphaYQ, a mutant of HbA

Template:ABSTRACT PUBMED 11724557

Disease

Known disease associated with this structure: Erythremias, alpha- OMIM:[141800], Heinz body anemias, alpha- OMIM:[141800], Methemoglobinemias, alpha- OMIM:[141800], Thalassemias, alpha- OMIM:[141800], Erythremias, beta- OMIM:[141900], HPFH, deletion type OMIM:[141900], Heinz body anemias, beta- OMIM:[141900], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, beta- OMIM:[141900]

About this Structure

1J7S is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Control of heme reactivity by diffusion: structural basis and functional characterization in hemoglobin mutants., Miele AE, Draghi F, Arcovito A, Bellelli A, Brunori M, Travaglini-Allocatelli C, Vallone B, Biochemistry. 2001 Dec 4;40(48):14449-58. PMID:11724557

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