1qi8
From Proteopedia
(New page: 200px<br /> <applet load="1qi8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qi8, resolution 1.8Å" /> '''DEOXYGENATED STRUCTU...) |
|||
| Line 6: | Line 6: | ||
==Overview== | ==Overview== | ||
Functional and structural studies on hemoglobin and myoglobin from, different animals and engineered variants have enlightened the great, importance of the physico-chemical properties of the side-chains at, topological position B10 and E7. These residues proved to be crucial to, the discrimination and stabilisation of gaseous ligands. In view of the, data obtained on the high oxygen affinity hemoglobin from Ascaris worms, and a new mutant of sperm whale myoglobin, we selected the two mutations, Leu B10-->Tyr and His E7-->Gln as potentially relevant to control ligand, binding parameters in the alpha and beta-chains of human hemoglobin. Here, we present an investigation of three new mutants: HbalphaYQ, (alpha2YQbeta2A), HbbetaYQ (alpha2Abeta2YQ) and HbalphabetaYQ, (alpha2YQbeta2YQ). They are characterised by a very low reactivity for NO, O2 and CO, and a reduced cooperativity. Their functional properties are, not inconsistent with the behaviour expected for a two-state allosteric, model. Proteins with these substitutions may be considered as candidates, for the synthesis of a possible "blood substitute", which should yield an, O2 adduct stable to autoxidation and slowly reacting with NO. The mutant, HbalphabetaYQ is particularly interesting because the rate of reaction of, NO with the oxy and deoxy derivatives is reduced. A structural, interpretation of our data is presented based on the 3D structure of deoxy, HbalphabetaYQ determined by crystallography at 1.8 A resolution. | Functional and structural studies on hemoglobin and myoglobin from, different animals and engineered variants have enlightened the great, importance of the physico-chemical properties of the side-chains at, topological position B10 and E7. These residues proved to be crucial to, the discrimination and stabilisation of gaseous ligands. In view of the, data obtained on the high oxygen affinity hemoglobin from Ascaris worms, and a new mutant of sperm whale myoglobin, we selected the two mutations, Leu B10-->Tyr and His E7-->Gln as potentially relevant to control ligand, binding parameters in the alpha and beta-chains of human hemoglobin. Here, we present an investigation of three new mutants: HbalphaYQ, (alpha2YQbeta2A), HbbetaYQ (alpha2Abeta2YQ) and HbalphabetaYQ, (alpha2YQbeta2YQ). They are characterised by a very low reactivity for NO, O2 and CO, and a reduced cooperativity. Their functional properties are, not inconsistent with the behaviour expected for a two-state allosteric, model. Proteins with these substitutions may be considered as candidates, for the synthesis of a possible "blood substitute", which should yield an, O2 adduct stable to autoxidation and slowly reacting with NO. The mutant, HbalphabetaYQ is particularly interesting because the rate of reaction of, NO with the oxy and deoxy derivatives is reduced. A structural, interpretation of our data is presented based on the 3D structure of deoxy, HbalphabetaYQ determined by crystallography at 1.8 A resolution. | ||
| + | |||
| + | ==Disease== | ||
| + | Known diseases associated with this structure: Erythremias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Erythremias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Erythrocytosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], HPFH, deletion type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Heinz body anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Heinz body anemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Heinz body anemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Hemoglobin H disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Hypochromic microcytic anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Methemoglobinemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Methemoglobinemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Sickle cell anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Thalassemia, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Thalassemia-beta, dominant inclusion-body OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Thalassemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Thalassemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 25: | Line 28: | ||
[[Category: low no reactivity]] | [[Category: low no reactivity]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:53:22 2007'' |
Revision as of 16:46, 12 November 2007
|
DEOXYGENATED STRUCTURE OF A DISTAL POCKET HEMOGLOBIN MUTANT
Contents |
Overview
Functional and structural studies on hemoglobin and myoglobin from, different animals and engineered variants have enlightened the great, importance of the physico-chemical properties of the side-chains at, topological position B10 and E7. These residues proved to be crucial to, the discrimination and stabilisation of gaseous ligands. In view of the, data obtained on the high oxygen affinity hemoglobin from Ascaris worms, and a new mutant of sperm whale myoglobin, we selected the two mutations, Leu B10-->Tyr and His E7-->Gln as potentially relevant to control ligand, binding parameters in the alpha and beta-chains of human hemoglobin. Here, we present an investigation of three new mutants: HbalphaYQ, (alpha2YQbeta2A), HbbetaYQ (alpha2Abeta2YQ) and HbalphabetaYQ, (alpha2YQbeta2YQ). They are characterised by a very low reactivity for NO, O2 and CO, and a reduced cooperativity. Their functional properties are, not inconsistent with the behaviour expected for a two-state allosteric, model. Proteins with these substitutions may be considered as candidates, for the synthesis of a possible "blood substitute", which should yield an, O2 adduct stable to autoxidation and slowly reacting with NO. The mutant, HbalphabetaYQ is particularly interesting because the rate of reaction of, NO with the oxy and deoxy derivatives is reduced. A structural, interpretation of our data is presented based on the 3D structure of deoxy, HbalphabetaYQ determined by crystallography at 1.8 A resolution.
Disease
Known diseases associated with this structure: Erythremias, alpha- OMIM:[141800], Erythremias, beta- OMIM:[141900], Erythrocytosis OMIM:[141850], HPFH, deletion type OMIM:[141900], Heinz body anemia OMIM:[141850], Heinz body anemias, alpha- OMIM:[141800], Heinz body anemias, beta- OMIM:[141900], Hemoglobin H disease OMIM:[141850], Hypochromic microcytic anemia OMIM:[141850], Methemoglobinemias, alpha- OMIM:[141800], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia, alpha- OMIM:[141850], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, alpha- OMIM:[141800], Thalassemias, beta- OMIM:[141900]
About this Structure
1QI8 is a Protein complex structure of sequences from Homo sapiens with HEM as ligand. Full crystallographic information is available from OCA.
Reference
Modulation of ligand binding in engineered human hemoglobin distal pocket., Miele AE, Santanche S, Travaglini-Allocatelli C, Vallone B, Brunori M, Bellelli A, J Mol Biol. 1999 Jul 9;290(2):515-24. PMID:10390349
Page seeded by OCA on Mon Nov 12 18:53:22 2007
