1vwt: Difference between revisions
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'''T STATE HUMAN HEMOGLOBIN [ALPHA V96W], ALPHA AQUOMET, BETA DEOXY''' | {{Structure | ||
|PDB= 1vwt |SIZE=350|CAPTION= <scene name='initialview01'>1vwt</scene>, resolution 1.9Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=HEM:PROTOPORPHYRIN IX CONTAINING FE'>HEM</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''T STATE HUMAN HEMOGLOBIN [ALPHA V96W], ALPHA AQUOMET, BETA DEOXY''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1VWT is a [ | 1VWT is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VWT OCA]. | ||
==Reference== | ==Reference== | ||
Novel water-mediated hydrogen bonds as the structural basis for the low oxygen affinity of the blood substitute candidate rHb(alpha 96Val-->Trp)., Puius YA, Zou M, Ho NT, Ho C, Almo SC, Biochemistry. 1998 Jun 30;37(26):9258-65. PMID:[http:// | Novel water-mediated hydrogen bonds as the structural basis for the low oxygen affinity of the blood substitute candidate rHb(alpha 96Val-->Trp)., Puius YA, Zou M, Ho NT, Ho C, Almo SC, Biochemistry. 1998 Jun 30;37(26):9258-65. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9649306 9649306] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: oxygen transport]] | [[Category: oxygen transport]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:49:32 2008'' | ||
Revision as of 15:49, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
T STATE HUMAN HEMOGLOBIN [ALPHA V96W], ALPHA AQUOMET, BETA DEOXY
OverviewOverview
One of the most promising approaches for the development of a synthetic blood substitute has been the engineering of novel mutants of human hemoglobin (Hb) A which maintain cooperativity, but possess lowered oxygen affinity. We describe here two crystal structures of one such potential blood substitute, recombinant (r) Hb(alpha 96Val-->Trp), refined to 1.9 A resolution in an alpha-aquomet, beta-deoxy T-state, and to 2.5 A resolution in a carbonmonoxy R-state. On the basis of molecular dynamics simulations, a particular conformation had been predicted for the engineered Trp residue, and the lowered oxygen affinity had been attributed to a stabilization of the deoxy T-state interface by alpha 96Trp-beta 99Asp hydrogen bonds. Difference Fourier maps of the T-state structure clearly show that alpha 96Trp is in a conformation different from that predicted by the simulation, with its indole side chain directed away from the interface and into the central cavity. In this conformation, the indole nitrogen makes novel water-mediated hydrogen bonds across the T-state interface with beta 101Glu. We propose that these water-mediated hydrogen bonds are the structural basis for the lowered oxygen affinity of rHb(alpha 96Val-->Trp), and discuss the implications of these findings for future molecular dynamics studies and the design of Hb mutants.
DiseaseDisease
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 StructureAbout this Structure
1VWT is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Novel water-mediated hydrogen bonds as the structural basis for the low oxygen affinity of the blood substitute candidate rHb(alpha 96Val-->Trp)., Puius YA, Zou M, Ho NT, Ho C, Almo SC, Biochemistry. 1998 Jun 30;37(26):9258-65. PMID:9649306
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