A Kinetic, Spectroscopic, and Redox Study of Human Tryptophan 2,3-Dioxygenase
The family of heme dioxygenases, as exemplified by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, catalyzes the oxidative cleavage of l-tryptophan to N-formylkynurenine. Here, we describe a bacterial expression system for human tryptophan 2,3-dioxygenase (rhTDO) together with spectrosco...
Gespeichert in:
| Veröffentlicht in: | Biochemistry (Easton) 2008-04, Vol.47 (16), p.4752-4760 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4760 |
|---|---|
| container_issue | 16 |
| container_start_page | 4752 |
| container_title | Biochemistry (Easton) |
| container_volume | 47 |
| creator | Basran, Jaswir Rafice, Sara A Chauhan, Nishma Efimov, Igor Cheesman, Myles R Ghamsari, Lila Raven, Emma Lloyd |
| description | The family of heme dioxygenases, as exemplified by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, catalyzes the oxidative cleavage of l-tryptophan to N-formylkynurenine. Here, we describe a bacterial expression system for human tryptophan 2,3-dioxygenase (rhTDO) together with spectroscopic, kinetic, and redox analyses. We find unexpected differences between human tryptophan 2,3-dioxygenase and human indoleamine 2,3-dioxygenase [Chauhan et al. (2008) Biochemistry 47, 4761−4769]. Thus, in contrast to indoleamine 2,3-dioxygenase, the catalytic ferrous−oxy complex of rhTDO is not observed, nor does the enzyme discriminate against substrate binding to the ferric derivative. In addition, we show that the rhTDO is also catalytically active in the ferric form. These new findings illustrate that significant mechanistic differences exist across the heme dioxygenase family, and the data are discussed within this broader framework. |
| doi_str_mv | 10.1021/bi702393b |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70773802</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70773802</sourcerecordid><originalsourceid>FETCH-LOGICAL-a417t-e45c2f3764faf46f4136819c57544c5348d7df4c46e0034f182687bef387d643</originalsourceid><addsrcrecordid>eNptkE1PwkAQhjdGI4ge_AOmF01MqO5Xd9sjQQEjRpTeN8t2V6vQrd02of_eJSV48TTvZJ7MZB4ALhG8QxCj-1XOISYJWR2BPoowDGmSRMegDyFkIU4Y7IEz5758SyGnp6CHYsJ9Rn3wMgqe80LXuRoGy1KrurJO2XLXyiIL3nVmt8GybrI2sCaYNRtZBGnVlrUtP33EQxI-5HbbfuhCOn0OToxcO32xrwOQTh7T8Sycv06fxqN5KCnidahppLAhnFEjDWWGIsJilKiIR5SqiNA445mhijINIaEGxZjFfKUNiXnGKBmAm25tWdmfRrtabHKn9HotC20bJzjknMReyQDcdqDyb7lKG1FW-UZWrUBQ7NSJgzrPXu2XNquNzv7IvSsPhB2Qu1pvD3NZfQvGCY9EuliK-WKK3_CUiInnrzteKie-bFMVXsk_h38BgjSBtw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70773802</pqid></control><display><type>article</type><title>A Kinetic, Spectroscopic, and Redox Study of Human Tryptophan 2,3-Dioxygenase</title><source>ACS Publications</source><source>MEDLINE</source><creator>Basran, Jaswir ; Rafice, Sara A ; Chauhan, Nishma ; Efimov, Igor ; Cheesman, Myles R ; Ghamsari, Lila ; Raven, Emma Lloyd</creator><creatorcontrib>Basran, Jaswir ; Rafice, Sara A ; Chauhan, Nishma ; Efimov, Igor ; Cheesman, Myles R ; Ghamsari, Lila ; Raven, Emma Lloyd</creatorcontrib><description>The family of heme dioxygenases, as exemplified by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, catalyzes the oxidative cleavage of l-tryptophan to N-formylkynurenine. Here, we describe a bacterial expression system for human tryptophan 2,3-dioxygenase (rhTDO) together with spectroscopic, kinetic, and redox analyses. We find unexpected differences between human tryptophan 2,3-dioxygenase and human indoleamine 2,3-dioxygenase [Chauhan et al. (2008) Biochemistry 47, 4761−4769]. Thus, in contrast to indoleamine 2,3-dioxygenase, the catalytic ferrous−oxy complex of rhTDO is not observed, nor does the enzyme discriminate against substrate binding to the ferric derivative. In addition, we show that the rhTDO is also catalytically active in the ferric form. These new findings illustrate that significant mechanistic differences exist across the heme dioxygenase family, and the data are discussed within this broader framework.</description><identifier>ISSN: 0006-2960</identifier><identifier>EISSN: 1520-4995</identifier><identifier>DOI: 10.1021/bi702393b</identifier><identifier>PMID: 18370401</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Electrons ; Gene Expression ; Humans ; Iron - metabolism ; Kinetics ; Ligands ; Molecular Structure ; Oxidation-Reduction ; Oxygen - metabolism ; Potentiometry ; Protein Binding ; Spectrophotometry ; Tryptophan - chemistry ; Tryptophan - metabolism ; Tryptophan Oxygenase - chemistry ; Tryptophan Oxygenase - genetics ; Tryptophan Oxygenase - isolation & purification ; Tryptophan Oxygenase - metabolism</subject><ispartof>Biochemistry (Easton), 2008-04, Vol.47 (16), p.4752-4760</ispartof><rights>Copyright © 2008 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a417t-e45c2f3764faf46f4136819c57544c5348d7df4c46e0034f182687bef387d643</citedby><cites>FETCH-LOGICAL-a417t-e45c2f3764faf46f4136819c57544c5348d7df4c46e0034f182687bef387d643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bi702393b$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bi702393b$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18370401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Basran, Jaswir</creatorcontrib><creatorcontrib>Rafice, Sara A</creatorcontrib><creatorcontrib>Chauhan, Nishma</creatorcontrib><creatorcontrib>Efimov, Igor</creatorcontrib><creatorcontrib>Cheesman, Myles R</creatorcontrib><creatorcontrib>Ghamsari, Lila</creatorcontrib><creatorcontrib>Raven, Emma Lloyd</creatorcontrib><title>A Kinetic, Spectroscopic, and Redox Study of Human Tryptophan 2,3-Dioxygenase</title><title>Biochemistry (Easton)</title><addtitle>Biochemistry</addtitle><description>The family of heme dioxygenases, as exemplified by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, catalyzes the oxidative cleavage of l-tryptophan to N-formylkynurenine. Here, we describe a bacterial expression system for human tryptophan 2,3-dioxygenase (rhTDO) together with spectroscopic, kinetic, and redox analyses. We find unexpected differences between human tryptophan 2,3-dioxygenase and human indoleamine 2,3-dioxygenase [Chauhan et al. (2008) Biochemistry 47, 4761−4769]. Thus, in contrast to indoleamine 2,3-dioxygenase, the catalytic ferrous−oxy complex of rhTDO is not observed, nor does the enzyme discriminate against substrate binding to the ferric derivative. In addition, we show that the rhTDO is also catalytically active in the ferric form. These new findings illustrate that significant mechanistic differences exist across the heme dioxygenase family, and the data are discussed within this broader framework.</description><subject>Electrons</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Iron - metabolism</subject><subject>Kinetics</subject><subject>Ligands</subject><subject>Molecular Structure</subject><subject>Oxidation-Reduction</subject><subject>Oxygen - metabolism</subject><subject>Potentiometry</subject><subject>Protein Binding</subject><subject>Spectrophotometry</subject><subject>Tryptophan - chemistry</subject><subject>Tryptophan - metabolism</subject><subject>Tryptophan Oxygenase - chemistry</subject><subject>Tryptophan Oxygenase - genetics</subject><subject>Tryptophan Oxygenase - isolation & purification</subject><subject>Tryptophan Oxygenase - metabolism</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1PwkAQhjdGI4ge_AOmF01MqO5Xd9sjQQEjRpTeN8t2V6vQrd02of_eJSV48TTvZJ7MZB4ALhG8QxCj-1XOISYJWR2BPoowDGmSRMegDyFkIU4Y7IEz5758SyGnp6CHYsJ9Rn3wMgqe80LXuRoGy1KrurJO2XLXyiIL3nVmt8GybrI2sCaYNRtZBGnVlrUtP33EQxI-5HbbfuhCOn0OToxcO32xrwOQTh7T8Sycv06fxqN5KCnidahppLAhnFEjDWWGIsJilKiIR5SqiNA445mhijINIaEGxZjFfKUNiXnGKBmAm25tWdmfRrtabHKn9HotC20bJzjknMReyQDcdqDyb7lKG1FW-UZWrUBQ7NSJgzrPXu2XNquNzv7IvSsPhB2Qu1pvD3NZfQvGCY9EuliK-WKK3_CUiInnrzteKie-bFMVXsk_h38BgjSBtw</recordid><startdate>20080422</startdate><enddate>20080422</enddate><creator>Basran, Jaswir</creator><creator>Rafice, Sara A</creator><creator>Chauhan, Nishma</creator><creator>Efimov, Igor</creator><creator>Cheesman, Myles R</creator><creator>Ghamsari, Lila</creator><creator>Raven, Emma Lloyd</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20080422</creationdate><title>A Kinetic, Spectroscopic, and Redox Study of Human Tryptophan 2,3-Dioxygenase</title><author>Basran, Jaswir ; Rafice, Sara A ; Chauhan, Nishma ; Efimov, Igor ; Cheesman, Myles R ; Ghamsari, Lila ; Raven, Emma Lloyd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a417t-e45c2f3764faf46f4136819c57544c5348d7df4c46e0034f182687bef387d643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Electrons</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Iron - metabolism</topic><topic>Kinetics</topic><topic>Ligands</topic><topic>Molecular Structure</topic><topic>Oxidation-Reduction</topic><topic>Oxygen - metabolism</topic><topic>Potentiometry</topic><topic>Protein Binding</topic><topic>Spectrophotometry</topic><topic>Tryptophan - chemistry</topic><topic>Tryptophan - metabolism</topic><topic>Tryptophan Oxygenase - chemistry</topic><topic>Tryptophan Oxygenase - genetics</topic><topic>Tryptophan Oxygenase - isolation & purification</topic><topic>Tryptophan Oxygenase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Basran, Jaswir</creatorcontrib><creatorcontrib>Rafice, Sara A</creatorcontrib><creatorcontrib>Chauhan, Nishma</creatorcontrib><creatorcontrib>Efimov, Igor</creatorcontrib><creatorcontrib>Cheesman, Myles R</creatorcontrib><creatorcontrib>Ghamsari, Lila</creatorcontrib><creatorcontrib>Raven, Emma Lloyd</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Basran, Jaswir</au><au>Rafice, Sara A</au><au>Chauhan, Nishma</au><au>Efimov, Igor</au><au>Cheesman, Myles R</au><au>Ghamsari, Lila</au><au>Raven, Emma Lloyd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Kinetic, Spectroscopic, and Redox Study of Human Tryptophan 2,3-Dioxygenase</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>2008-04-22</date><risdate>2008</risdate><volume>47</volume><issue>16</issue><spage>4752</spage><epage>4760</epage><pages>4752-4760</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>The family of heme dioxygenases, as exemplified by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, catalyzes the oxidative cleavage of l-tryptophan to N-formylkynurenine. Here, we describe a bacterial expression system for human tryptophan 2,3-dioxygenase (rhTDO) together with spectroscopic, kinetic, and redox analyses. We find unexpected differences between human tryptophan 2,3-dioxygenase and human indoleamine 2,3-dioxygenase [Chauhan et al. (2008) Biochemistry 47, 4761−4769]. Thus, in contrast to indoleamine 2,3-dioxygenase, the catalytic ferrous−oxy complex of rhTDO is not observed, nor does the enzyme discriminate against substrate binding to the ferric derivative. In addition, we show that the rhTDO is also catalytically active in the ferric form. These new findings illustrate that significant mechanistic differences exist across the heme dioxygenase family, and the data are discussed within this broader framework.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>18370401</pmid><doi>10.1021/bi702393b</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-2960 |
| ispartof | Biochemistry (Easton), 2008-04, Vol.47 (16), p.4752-4760 |
| issn | 0006-2960 1520-4995 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70773802 |
| source | ACS Publications; MEDLINE |
| subjects | Electrons Gene Expression Humans Iron - metabolism Kinetics Ligands Molecular Structure Oxidation-Reduction Oxygen - metabolism Potentiometry Protein Binding Spectrophotometry Tryptophan - chemistry Tryptophan - metabolism Tryptophan Oxygenase - chemistry Tryptophan Oxygenase - genetics Tryptophan Oxygenase - isolation & purification Tryptophan Oxygenase - metabolism |
| title | A Kinetic, Spectroscopic, and Redox Study of Human Tryptophan 2,3-Dioxygenase |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T21%3A36%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Kinetic,%20Spectroscopic,%20and%20Redox%20Study%20of%20Human%20Tryptophan%202,3-Dioxygenase&rft.jtitle=Biochemistry%20(Easton)&rft.au=Basran,%20Jaswir&rft.date=2008-04-22&rft.volume=47&rft.issue=16&rft.spage=4752&rft.epage=4760&rft.pages=4752-4760&rft.issn=0006-2960&rft.eissn=1520-4995&rft_id=info:doi/10.1021/bi702393b&rft_dat=%3Cproquest_cross%3E70773802%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70773802&rft_id=info:pmid/18370401&rfr_iscdi=true |