Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase
Zinc thiolate complexes containing N[subscript 2]S tridentate ligands were prepared to investigate their reactivity toward reactive nitrogen species, chemistry proposed to occur at the zinc tetracysteine thiolate site of nitric oxide synthase (NOS). The complexes are unreactive toward nitric oxide (...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2013
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| Online Access: | http://hdl.handle.net/1721.1/82152 https://orcid.org/0000-0002-2693-4982 |
| _version_ | 1811075677481336832 |
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| author | Kozhukh, Julia Lippard, Stephen J. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Kozhukh, Julia Lippard, Stephen J. |
| author_sort | Kozhukh, Julia |
| collection | MIT |
| description | Zinc thiolate complexes containing N[subscript 2]S tridentate ligands were prepared to investigate their reactivity toward reactive nitrogen species, chemistry proposed to occur at the zinc tetracysteine thiolate site of nitric oxide synthase (NOS). The complexes are unreactive toward nitric oxide (NO) in the absence of dioxygen, strongly indicating that NO cannot be the species directly responsible for S-nitrosothiol formation and loss of Zn[superscript 2+] at the NOS dimer interface in vivo. S-Nitrosothiol formation does occur upon exposure of zinc thiolate solutions to NO in the presence of air, however, or to NO[subscript 2] or NOBF[subscript 4], indicating that these reactive nitrogen/oxygen species are capable of liberating zinc from the enzyme, possibly through generation of the S-nitrosothiol. Interaction between simple Zn[superscript 2+] salts and preformed S-nitrosothiols leads to decomposition of the −SNO moiety, resulting in release of gaseous NO and N[subscript 2]O. The potential biological relevance of this chemistry is discussed. |
| first_indexed | 2024-09-23T10:10:10Z |
| format | Article |
| id | mit-1721.1/82152 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:10:10Z |
| publishDate | 2013 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/821522022-09-30T19:19:56Z Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase Kozhukh, Julia Lippard, Stephen J. Massachusetts Institute of Technology. Department of Chemistry Kozhukh, Julia Lippard, Stephen J. Zinc thiolate complexes containing N[subscript 2]S tridentate ligands were prepared to investigate their reactivity toward reactive nitrogen species, chemistry proposed to occur at the zinc tetracysteine thiolate site of nitric oxide synthase (NOS). The complexes are unreactive toward nitric oxide (NO) in the absence of dioxygen, strongly indicating that NO cannot be the species directly responsible for S-nitrosothiol formation and loss of Zn[superscript 2+] at the NOS dimer interface in vivo. S-Nitrosothiol formation does occur upon exposure of zinc thiolate solutions to NO in the presence of air, however, or to NO[subscript 2] or NOBF[subscript 4], indicating that these reactive nitrogen/oxygen species are capable of liberating zinc from the enzyme, possibly through generation of the S-nitrosothiol. Interaction between simple Zn[superscript 2+] salts and preformed S-nitrosothiols leads to decomposition of the −SNO moiety, resulting in release of gaseous NO and N[subscript 2]O. The potential biological relevance of this chemistry is discussed. National Science Foundation (U.S.) (Grant CHE0907905) National Institutes of Health (U.S.) (Grant 1A10RR013886-01) 2013-11-18T13:43:29Z 2013-11-18T13:43:29Z 2012-06 2012-04 Article http://purl.org/eprint/type/JournalArticle 0020-1669 1520-510X http://hdl.handle.net/1721.1/82152 Kozhukh, Julia, and Stephen J. Lippard. “Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn2+ with S-Nitrosothiols and Implications for Nitric Oxide Synthase.” Inorganic Chemistry 51, no. 13 (July 2, 2012): 7346-7353. https://orcid.org/0000-0002-2693-4982 en_US http://dx.doi.org/10.1021/ic3007684 Inorganic Chemistry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Kozhukh, Julia Lippard, Stephen J. Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase |
| title | Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase |
| title_full | Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase |
| title_fullStr | Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase |
| title_full_unstemmed | Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase |
| title_short | Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S-Nitrosothiols and Implications for Nitric Oxide Synthase |
| title_sort | zinc thiolate reactivity toward nitrogen oxides insights into the interaction of zn superscript 2 with s nitrosothiols and implications for nitric oxide synthase |
| url | http://hdl.handle.net/1721.1/82152 https://orcid.org/0000-0002-2693-4982 |
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