A cis -Proline in $\alpha$-Hemoglobin Stabilizing Protein Directs the Structural Reorganization of $\alpha$-Hemoglobin. Gell, D. A., Feng, L., Zhou, S., Jeffrey, P. D., Bendak, K., Gow, A., Weiss, M. J., Shi, Y., & Mackay, J. P. Journal of Biological Chemistry, 284(43):29462–29469, oct, 2009.
Paper doi abstract bibtex $\alpha$-Hemoglobin ($\alpha$Hb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with $\alpha$Hb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting $\alpha$Hb 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 $\alpha$Hb 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 $\alpha$Hb. In complex with-Hb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in $\alpha$Hb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the $\alpha$Hb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of $\alpha$Hb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. \textcopyright 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
@article{Gell2009,
abstract = {$\alpha$-Hemoglobin ($\alpha$Hb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with $\alpha$Hb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting $\alpha$Hb 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 $\alpha$Hb 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 $\alpha$Hb. In complex with-Hb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in $\alpha$Hb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the $\alpha$Hb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of $\alpha$Hb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. {\textcopyright} 2009 by The American Society for Biochemistry and Molecular Biology, Inc.},
annote = {cited By 16},
author = {Gell, David A. and Feng, Liang and Zhou, Suiping and Jeffrey, Philip D. and Bendak, Katerina and Gow, Andrew and Weiss, Mitchell J. and Shi, Yigong and Mackay, Joel P.},
doi = {10.1074/jbc.M109.027045},
issn = {0021-9258},
journal = {Journal of Biological Chemistry},
month = {oct},
number = {43},
pages = {29462--29469},
pmid = {19706593},
title = {{A cis -Proline in $\alpha$-Hemoglobin Stabilizing Protein Directs the Structural Reorganization of $\alpha$-Hemoglobin}},
url = {http://www.jbc.org/lookup/doi/10.1074/jbc.M109.027045},
volume = {284},
year = {2009}
}
Downloads: 0
{"_id":"p336Zp5fLMzNqBWxT","bibbaseid":"gell-feng-zhou-jeffrey-bendak-gow-weiss-shi-etal-acisprolineinalphahemoglobinstabilizingproteindirectsthestructuralreorganizationofalphahemoglobin-2009","authorIDs":[],"author_short":["Gell, D. A.","Feng, L.","Zhou, S.","Jeffrey, P. D.","Bendak, K.","Gow, A.","Weiss, M. J.","Shi, Y.","Mackay, J. P."],"bibdata":{"bibtype":"article","type":"article","abstract":"$\\alpha$-Hemoglobin ($\\alpha$Hb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with $\\alpha$Hb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting $\\alpha$Hb 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 $\\alpha$Hb 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 $\\alpha$Hb. In complex with-Hb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in $\\alpha$Hb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the $\\alpha$Hb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of $\\alpha$Hb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. \\textcopyright 2009 by The American Society for Biochemistry and Molecular Biology, Inc.","annote":"cited By 16","author":[{"propositions":[],"lastnames":["Gell"],"firstnames":["David","A."],"suffixes":[]},{"propositions":[],"lastnames":["Feng"],"firstnames":["Liang"],"suffixes":[]},{"propositions":[],"lastnames":["Zhou"],"firstnames":["Suiping"],"suffixes":[]},{"propositions":[],"lastnames":["Jeffrey"],"firstnames":["Philip","D."],"suffixes":[]},{"propositions":[],"lastnames":["Bendak"],"firstnames":["Katerina"],"suffixes":[]},{"propositions":[],"lastnames":["Gow"],"firstnames":["Andrew"],"suffixes":[]},{"propositions":[],"lastnames":["Weiss"],"firstnames":["Mitchell","J."],"suffixes":[]},{"propositions":[],"lastnames":["Shi"],"firstnames":["Yigong"],"suffixes":[]},{"propositions":[],"lastnames":["Mackay"],"firstnames":["Joel","P."],"suffixes":[]}],"doi":"10.1074/jbc.M109.027045","issn":"0021-9258","journal":"Journal of Biological Chemistry","month":"oct","number":"43","pages":"29462–29469","pmid":"19706593","title":"A cis -Proline in $\\alpha$-Hemoglobin Stabilizing Protein Directs the Structural Reorganization of $\\alpha$-Hemoglobin","url":"http://www.jbc.org/lookup/doi/10.1074/jbc.M109.027045","volume":"284","year":"2009","bibtex":"@article{Gell2009,\nabstract = {$\\alpha$-Hemoglobin ($\\alpha$Hb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with $\\alpha$Hb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting $\\alpha$Hb 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 $\\alpha$Hb 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 $\\alpha$Hb. In complex with-Hb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in $\\alpha$Hb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the $\\alpha$Hb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of $\\alpha$Hb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. {\\textcopyright} 2009 by The American Society for Biochemistry and Molecular Biology, Inc.},\nannote = {cited By 16},\nauthor = {Gell, David A. and Feng, Liang and Zhou, Suiping and Jeffrey, Philip D. and Bendak, Katerina and Gow, Andrew and Weiss, Mitchell J. and Shi, Yigong and Mackay, Joel P.},\ndoi = {10.1074/jbc.M109.027045},\nissn = {0021-9258},\njournal = {Journal of Biological Chemistry},\nmonth = {oct},\nnumber = {43},\npages = {29462--29469},\npmid = {19706593},\ntitle = {{A cis -Proline in $\\alpha$-Hemoglobin Stabilizing Protein Directs the Structural Reorganization of $\\alpha$-Hemoglobin}},\nurl = {http://www.jbc.org/lookup/doi/10.1074/jbc.M109.027045},\nvolume = {284},\nyear = {2009}\n}\n","author_short":["Gell, D. A.","Feng, L.","Zhou, S.","Jeffrey, P. D.","Bendak, K.","Gow, A.","Weiss, M. J.","Shi, Y.","Mackay, J. P."],"key":"Gell2009","id":"Gell2009","bibbaseid":"gell-feng-zhou-jeffrey-bendak-gow-weiss-shi-etal-acisprolineinalphahemoglobinstabilizingproteindirectsthestructuralreorganizationofalphahemoglobin-2009","role":"author","urls":{"Paper":"http://www.jbc.org/lookup/doi/10.1074/jbc.M109.027045"},"downloads":0},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1EvkYjMfb1LmGOV8-ek4_e6g77kIA7ABa","creationDate":"2020-12-14T07:58:48.496Z","downloads":0,"keywords":[],"search_terms":["cis","proline","alpha","hemoglobin","stabilizing","protein","directs","structural","reorganization","alpha","hemoglobin","gell","feng","zhou","jeffrey","bendak","gow","weiss","shi","mackay"],"title":"A cis -Proline in $\\alpha$-Hemoglobin Stabilizing Protein Directs the Structural Reorganization of $\\alpha$-Hemoglobin","year":2009,"dataSources":["QNo3CKhtog6c3sh7Y"]}