A cis-proline in α-hemoglobin stabilizing protein directs the structural reorganization of α-hemoglobin. Gell, D., Feng, L., Zhou, S., Jeffrey, P., Bendak, K., Gow, A., Weiss, M., Shi, Y., & Mackay, J. Journal of Biological Chemistry, 284(43):29462-29469, 2009.
doi  abstract   bibtex   
α-Hemoglobin (αHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with αHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting αHb to a conformation in which the heme is coordinated at both axial positions by histidine side chains (bis-histidyl coordination). Currently, the detailed mechanism by which AHSP induces structural changes in αHb has not been determined. Here, we present x-ray crystallography, NMR spectroscopy, and mutagenesis data that identify, for the first time, the importance of an evolutionarily conserved proline, Pro30, in loop 1 of AHSP. Mutation of Pro30 to a variety of residue types results in reduced ability to convert αHb. In complex with-Hb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in αHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the αHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of αHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
@article{
 title = {A cis-proline in α-hemoglobin stabilizing protein directs the structural reorganization of α-hemoglobin},
 type = {article},
 year = {2009},
 pages = {29462-29469},
 volume = {284},
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 abstract = {α-Hemoglobin (αHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with αHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting αHb to a conformation in which the heme is coordinated at both axial positions by histidine side chains (bis-histidyl coordination). Currently, the detailed mechanism by which AHSP induces structural changes in αHb has not been determined. Here, we present x-ray crystallography, NMR spectroscopy, and mutagenesis data that identify, for the first time, the importance of an evolutionarily conserved proline, Pro30, in loop 1 of AHSP. Mutation of Pro30 to a variety of residue types results in reduced ability to convert αHb. In complex with-Hb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in αHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the αHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of αHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.},
 bibtype = {article},
 author = {Gell, D.A. and Feng, L. and Zhou, S. and Jeffrey, P.D. and Bendak, K. and Gow, A. and Weiss, M.J. and Shi, Y. and Mackay, J.P.},
 doi = {10.1074/jbc.M109.027045},
 journal = {Journal of Biological Chemistry},
 number = {43}
}

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