1w0a
SOLUTION STRUCTURE OF THE TRANS FORM OF THE HUMAN ALPHA-HEMOGLOBIN STABILIZING PROTEIN (AHSP)
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OverviewOverview
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.
About this StructureAbout this Structure
1W0A is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
NMR structure of the alpha-hemoglobin stabilizing protein: insights into conformational heterogeneity and binding., Santiveri CM, Perez-Canadillas JM, Vadivelu MK, Allen MD, Rutherford TJ, Watkins NA, Bycroft M, J Biol Chem. 2004 Aug 13;279(33):34963-70. Epub 2004 Jun 3. PMID:15178680
Page seeded by OCA on Mon Nov 12 19:45:23 2007