STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS
The structural factors governing azide and cyanide binding have been examined by measuring the effects of 46 mutations at key topological positions in the distal pocket in sperm whale, pig, and human myoglobin. Replacement of His(64)(E7) with smaller amino acids results in dramatic increases in the...
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AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
1994
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ftunivromairis:oai:iris.uniroma1.it:11573/406559 2024-04-14T08:20:08+00:00 STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS A. Brancaccio S. J. Smerdon A. J. Wilkinson Y. Dou D. Keenan M. Ikeda Saito R. E. Jr Brantley J. S. Olson CUTRUZZOLA', Francesca TRAVAGLINI ALLOCATELLI, Carlo BRUNORI, Maurizio A., Brancaccio Cutruzzola', Francesca TRAVAGLINI ALLOCATELLI, Carlo Brunori, Maurizio S. J., Smerdon A. J., Wilkinson Y., Dou D., Keenan M., Ikeda Saito R. E., Jr Brantley J. S., Olson 1994 http://hdl.handle.net/11573/406559 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=A1994NL60600022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0028217656&partnerID=65&md5=f9aac3393862fc27f1454bb7d04e1fc8 eng eng AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC info:eu-repo/semantics/altIdentifier/pmid/8188662 info:eu-repo/semantics/altIdentifier/wos/WOS:A1994NL60600022 volume:269 issue:19 firstpage:13843 lastpage:13853 numberofpages:11 journal:THE JOURNAL OF BIOLOGICAL CHEMISTRY http://hdl.handle.net/11573/406559 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0028217656 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=A1994NL60600022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0028217656&partnerID=65&md5=f9aac3393862fc27f1454bb7d04e1fc8 info:eu-repo/semantics/article 1994 ftunivromairis 2024-03-21T19:27:56Z The structural factors governing azide and cyanide binding have been examined by measuring the effects of 46 mutations at key topological positions in the distal pocket in sperm whale, pig, and human myoglobin. Replacement of His(64)(E7) with smaller amino acids results in dramatic increases in the association rate constant for azide binding primarily due to relief of steric hindrance imposed by the imidazole side chain. Gln(64) and His(64) (native) metmyoglobins have abnormally low rate constants for azide dissociation (0.1-0.3 s(-1)) due to direct hydrogen bonding between the N-epsilon atoms of these residues and the bound ligand. Mutations at positions 67(E10) and 68(E11) produce large but complex changes in the azide binding parameters as a result of both steric and electrostatic effects, which alter water coordination, influence the rate of anion movement into the distal pocket, and affect the stability of the Fe-N-3 bond. Replacement of Phe(46) with Leu or Val and substitution of Arg(Lys)45 with Glu and Ser cause disorder in the position of the distal histidine side chain and result in 4-700-fold increases in both k'(N3) and k(N3) but produce little ohange in overall azide affinity. All of these results suggest strongly that azide enters the distal pocket of native myoglobin through a polar channel that is regulated by a His(64) ''gate.'' In contrast to azide binding, the rate constant for cyanide association decreases 4-300-fold when the distal histidine is replaced with apolar residues. His(64), Gln(64), and distal pocket water molecules appear to facilitate deprotonation of HCN, which is the major kinetic barrier to cyanide binding at neutral pH. Article in Journal/Newspaper Sperm whale Sapienza Università di Roma: CINECA IRIS |
institution |
Open Polar |
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Sapienza Università di Roma: CINECA IRIS |
op_collection_id |
ftunivromairis |
language |
English |
description |
The structural factors governing azide and cyanide binding have been examined by measuring the effects of 46 mutations at key topological positions in the distal pocket in sperm whale, pig, and human myoglobin. Replacement of His(64)(E7) with smaller amino acids results in dramatic increases in the association rate constant for azide binding primarily due to relief of steric hindrance imposed by the imidazole side chain. Gln(64) and His(64) (native) metmyoglobins have abnormally low rate constants for azide dissociation (0.1-0.3 s(-1)) due to direct hydrogen bonding between the N-epsilon atoms of these residues and the bound ligand. Mutations at positions 67(E10) and 68(E11) produce large but complex changes in the azide binding parameters as a result of both steric and electrostatic effects, which alter water coordination, influence the rate of anion movement into the distal pocket, and affect the stability of the Fe-N-3 bond. Replacement of Phe(46) with Leu or Val and substitution of Arg(Lys)45 with Glu and Ser cause disorder in the position of the distal histidine side chain and result in 4-700-fold increases in both k'(N3) and k(N3) but produce little ohange in overall azide affinity. All of these results suggest strongly that azide enters the distal pocket of native myoglobin through a polar channel that is regulated by a His(64) ''gate.'' In contrast to azide binding, the rate constant for cyanide association decreases 4-300-fold when the distal histidine is replaced with apolar residues. His(64), Gln(64), and distal pocket water molecules appear to facilitate deprotonation of HCN, which is the major kinetic barrier to cyanide binding at neutral pH. |
author2 |
A., Brancaccio Cutruzzola', Francesca TRAVAGLINI ALLOCATELLI, Carlo Brunori, Maurizio S. J., Smerdon A. J., Wilkinson Y., Dou D., Keenan M., Ikeda Saito R. E., Jr Brantley J. S., Olson |
format |
Article in Journal/Newspaper |
author |
A. Brancaccio S. J. Smerdon A. J. Wilkinson Y. Dou D. Keenan M. Ikeda Saito R. E. Jr Brantley J. S. Olson CUTRUZZOLA', Francesca TRAVAGLINI ALLOCATELLI, Carlo BRUNORI, Maurizio |
spellingShingle |
A. Brancaccio S. J. Smerdon A. J. Wilkinson Y. Dou D. Keenan M. Ikeda Saito R. E. Jr Brantley J. S. Olson CUTRUZZOLA', Francesca TRAVAGLINI ALLOCATELLI, Carlo BRUNORI, Maurizio STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS |
author_facet |
A. Brancaccio S. J. Smerdon A. J. Wilkinson Y. Dou D. Keenan M. Ikeda Saito R. E. Jr Brantley J. S. Olson CUTRUZZOLA', Francesca TRAVAGLINI ALLOCATELLI, Carlo BRUNORI, Maurizio |
author_sort |
A. Brancaccio |
title |
STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS |
title_short |
STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS |
title_full |
STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS |
title_fullStr |
STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS |
title_full_unstemmed |
STRUCTURAL FACTORS GOVERNING AZIDE AND CYANIDE BINDING TO MAMMALIAN METMYOGLOBINS |
title_sort |
structural factors governing azide and cyanide binding to mammalian metmyoglobins |
publisher |
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
publishDate |
1994 |
url |
http://hdl.handle.net/11573/406559 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=A1994NL60600022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0028217656&partnerID=65&md5=f9aac3393862fc27f1454bb7d04e1fc8 |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/8188662 info:eu-repo/semantics/altIdentifier/wos/WOS:A1994NL60600022 volume:269 issue:19 firstpage:13843 lastpage:13853 numberofpages:11 journal:THE JOURNAL OF BIOLOGICAL CHEMISTRY http://hdl.handle.net/11573/406559 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0028217656 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=A1994NL60600022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a http://www.scopus.com/inward/record.url?eid=2-s2.0-0028217656&partnerID=65&md5=f9aac3393862fc27f1454bb7d04e1fc8 |
_version_ |
1796298337236811776 |