Modulation of ligand binding in engineered human hemoglobin distal pocket
Functional and structural studies on hemoglobin and myoglobin from different animals and engineered variants have enlightened the great importance of the physico-chemical properties of the side-chains at topological position B10 and E7. These residues proved to be crucial to the discrimination and s...
Published in: | Journal of Molecular Biology |
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ACADEMIC PRESS LTD
1999
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Online Access: | http://hdl.handle.net/11573/241607 https://doi.org/10.1006/jmbi.1999.2869 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000081533600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0033538508&partnerID=65&md5=3093e1622e39e3ffa33ea6cda0c1f506 |
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ftunivromairis:oai:iris.uniroma1.it:11573/241607 2024-04-14T08:20:08+00:00 Modulation of ligand binding in engineered human hemoglobin distal pocket MIELE, Adriana Erica TRAVAGLINI ALLOCATELLI, Carlo VALLONE, Beatrice BRUNORI, Maurizio BELLELLI, Andrea S. Santanche' Miele, Adriana Erica S., Santanche' TRAVAGLINI ALLOCATELLI, Carlo Vallone, Beatrice Brunori, Maurizio Bellelli, Andrea 1999 http://hdl.handle.net/11573/241607 https://doi.org/10.1006/jmbi.1999.2869 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000081533600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0033538508&partnerID=65&md5=3093e1622e39e3ffa33ea6cda0c1f506 eng eng ACADEMIC PRESS LTD info:eu-repo/semantics/altIdentifier/pmid/10390349 info:eu-repo/semantics/altIdentifier/wos/WOS:000081533600014 volume:290 issue:2 firstpage:515 lastpage:524 numberofpages:10 journal:JOURNAL OF MOLECULAR BIOLOGY http://hdl.handle.net/11573/241607 doi:10.1006/jmbi.1999.2869 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0033538508 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000081533600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0033538508&partnerID=65&md5=3093e1622e39e3ffa33ea6cda0c1f506 allosteric regulation allosteric transition blood substitute crystallography hemoglobin protein crystallography site directed mutagenesi site-directed mutagenesis info:eu-repo/semantics/article 1999 ftunivromairis https://doi.org/10.1006/jmbi.1999.2869 2024-03-21T18:42:40Z Functional and structural studies on hemoglobin and myoglobin from different animals and engineered variants have enlightened the great importance of the physico-chemical properties of the side-chains at topological position B10 and E7. These residues proved to be crucial to the discrimination and stabilisation of gaseous ligands. Ln view of the data obtained on the high oxygen affinity hemoglobin from Ascaris worms and a new mutant of sperm whale myoglobin, we selected the two mutations Leu B10 --> Tyr and His E7 --> Gin as potentially relevant to control ligand binding parameters in the alpha and beta-chains of human hemoglobin. Here, we present an investigation of three new mutants: Hb alpha YQ (alpha(2)(YQ)beta(2)(A)), Hb beta YQ (alpha(2)(A)beta(2)(YQ)) and Hb alpha beta YQ (alpha(2)(YQ)beta(2)(YQ)). They are characterised by a very low reactivity for NO, O-2 and CO, and a reduced cooperativity. Their functional properties are not inconsistent with the behaviour expected for a two-state allosteric model. Proteins with these substitutions may be considered as candidates for the synthesis of a possible "blood substitute", which should yield an O-2 adduct stable to autoxidation and slowly reacting with NO. The mutant Hb alpha beta YQ is particularly interesting because the rate of reaction of NO with the oxy and deoxy derivatives is reduced. A structural interpretation of our data is presented based on the 3D structure of deoxy Hb alpha beta YQ determined by crystallography at 1:8 Angstrom resolution. (C) 1999 Academic Press. Article in Journal/Newspaper Sperm whale Sapienza Università di Roma: CINECA IRIS Journal of Molecular Biology 290 2 515 524 |
institution |
Open Polar |
collection |
Sapienza Università di Roma: CINECA IRIS |
op_collection_id |
ftunivromairis |
language |
English |
topic |
allosteric regulation allosteric transition blood substitute crystallography hemoglobin protein crystallography site directed mutagenesi site-directed mutagenesis |
spellingShingle |
allosteric regulation allosteric transition blood substitute crystallography hemoglobin protein crystallography site directed mutagenesi site-directed mutagenesis MIELE, Adriana Erica TRAVAGLINI ALLOCATELLI, Carlo VALLONE, Beatrice BRUNORI, Maurizio BELLELLI, Andrea S. Santanche' Modulation of ligand binding in engineered human hemoglobin distal pocket |
topic_facet |
allosteric regulation allosteric transition blood substitute crystallography hemoglobin protein crystallography site directed mutagenesi site-directed mutagenesis |
description |
Functional and structural studies on hemoglobin and myoglobin from different animals and engineered variants have enlightened the great importance of the physico-chemical properties of the side-chains at topological position B10 and E7. These residues proved to be crucial to the discrimination and stabilisation of gaseous ligands. Ln view of the data obtained on the high oxygen affinity hemoglobin from Ascaris worms and a new mutant of sperm whale myoglobin, we selected the two mutations Leu B10 --> Tyr and His E7 --> Gin as potentially relevant to control ligand binding parameters in the alpha and beta-chains of human hemoglobin. Here, we present an investigation of three new mutants: Hb alpha YQ (alpha(2)(YQ)beta(2)(A)), Hb beta YQ (alpha(2)(A)beta(2)(YQ)) and Hb alpha beta YQ (alpha(2)(YQ)beta(2)(YQ)). They are characterised by a very low reactivity for NO, O-2 and CO, and a reduced cooperativity. Their functional properties are not inconsistent with the behaviour expected for a two-state allosteric model. Proteins with these substitutions may be considered as candidates for the synthesis of a possible "blood substitute", which should yield an O-2 adduct stable to autoxidation and slowly reacting with NO. The mutant Hb alpha beta YQ is particularly interesting because the rate of reaction of NO with the oxy and deoxy derivatives is reduced. A structural interpretation of our data is presented based on the 3D structure of deoxy Hb alpha beta YQ determined by crystallography at 1:8 Angstrom resolution. (C) 1999 Academic Press. |
author2 |
Miele, Adriana Erica S., Santanche' TRAVAGLINI ALLOCATELLI, Carlo Vallone, Beatrice Brunori, Maurizio Bellelli, Andrea |
format |
Article in Journal/Newspaper |
author |
MIELE, Adriana Erica TRAVAGLINI ALLOCATELLI, Carlo VALLONE, Beatrice BRUNORI, Maurizio BELLELLI, Andrea S. Santanche' |
author_facet |
MIELE, Adriana Erica TRAVAGLINI ALLOCATELLI, Carlo VALLONE, Beatrice BRUNORI, Maurizio BELLELLI, Andrea S. Santanche' |
author_sort |
MIELE, Adriana Erica |
title |
Modulation of ligand binding in engineered human hemoglobin distal pocket |
title_short |
Modulation of ligand binding in engineered human hemoglobin distal pocket |
title_full |
Modulation of ligand binding in engineered human hemoglobin distal pocket |
title_fullStr |
Modulation of ligand binding in engineered human hemoglobin distal pocket |
title_full_unstemmed |
Modulation of ligand binding in engineered human hemoglobin distal pocket |
title_sort |
modulation of ligand binding in engineered human hemoglobin distal pocket |
publisher |
ACADEMIC PRESS LTD |
publishDate |
1999 |
url |
http://hdl.handle.net/11573/241607 https://doi.org/10.1006/jmbi.1999.2869 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000081533600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0033538508&partnerID=65&md5=3093e1622e39e3ffa33ea6cda0c1f506 |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/10390349 info:eu-repo/semantics/altIdentifier/wos/WOS:000081533600014 volume:290 issue:2 firstpage:515 lastpage:524 numberofpages:10 journal:JOURNAL OF MOLECULAR BIOLOGY http://hdl.handle.net/11573/241607 doi:10.1006/jmbi.1999.2869 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0033538508 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000081533600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0033538508&partnerID=65&md5=3093e1622e39e3ffa33ea6cda0c1f506 |
op_doi |
https://doi.org/10.1006/jmbi.1999.2869 |
container_title |
Journal of Molecular Biology |
container_volume |
290 |
container_issue |
2 |
container_start_page |
515 |
op_container_end_page |
524 |
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1796298339267903488 |