|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
33
|
|
pubmed:dateCreated |
2004-8-9
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
The structure of alpha-hemoglobin stabilizing protein (AHSP), a molecular chaperone for free alpha-hemoglobin, has been determined using NMR spectroscopy. The protein native state shows conformational heterogeneity attributable to the isomerization of the peptide bond preceding a conserved proline residue. The two equally populated cis and trans forms both adopt an elongated antiparallel three alpha-helix bundle fold but display major differences in the loop between the first two helices and at the C terminus of helix 3. Proline to alanine single point mutation of the residue Pro-30 prevents the cis/trans isomerization. The structure of the P30A mutant is similar to the structure of the trans form of AHSP in the loop 1 region. Both the wild-type AHSP and the P30A mutant bind to alpha-hemoglobin, and the wild-type conformational heterogeneity is quenched upon complex formation, suggesting that just one conformation is the active form. Changes in chemical shift observed upon complex formation identify a binding interface comprising the C terminus of helix 1, the loop 1, and the N terminus of helix 2, with the exposed residues Phe-47 and Tyr-51 being attractive targets for molecular recognition. The characteristics of this interface suggest that AHSP binds at the intradimer alpha1beta1 interface in tetrameric HbA.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/ERAF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
13
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
34963-70
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:15178680-Alanine,
pubmed-meshheading:15178680-Binding Sites,
pubmed-meshheading:15178680-Blood Proteins,
pubmed-meshheading:15178680-Cloning, Molecular,
pubmed-meshheading:15178680-DNA,
pubmed-meshheading:15178680-DNA, Complementary,
pubmed-meshheading:15178680-Dimerization,
pubmed-meshheading:15178680-Gene Library,
pubmed-meshheading:15178680-Humans,
pubmed-meshheading:15178680-Ligands,
pubmed-meshheading:15178680-Magnetic Resonance Spectroscopy,
pubmed-meshheading:15178680-Models, Molecular,
pubmed-meshheading:15178680-Molecular Chaperones,
pubmed-meshheading:15178680-Mutation,
pubmed-meshheading:15178680-Plasmids,
pubmed-meshheading:15178680-Point Mutation,
pubmed-meshheading:15178680-Proline,
pubmed-meshheading:15178680-Protein Binding,
pubmed-meshheading:15178680-Protein Conformation,
pubmed-meshheading:15178680-Protein Isoforms,
pubmed-meshheading:15178680-Protein Structure, Secondary,
pubmed-meshheading:15178680-Protein Structure, Tertiary,
pubmed-meshheading:15178680-Tyrosine
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
NMR structure of the alpha-hemoglobin stabilizing protein: insights into conformational heterogeneity and binding.
|
|
pubmed:affiliation |
Medical Research Council Centre for Protein Engineering, Hills Road, Cambridge CB2 2QH, United Kingdom.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
