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dc.contributor.authorBrock, Thomas G.en_US
dc.contributor.authorGale, Daviden_US
dc.contributor.authorHemak, Jasonen_US
dc.date.accessioned2006-09-11T19:29:46Z
dc.date.available2006-09-11T19:29:46Z
dc.date.issued2002-04en_US
dc.identifier.citationHemak, Jason; Gale, David; Brock, Thomas G.; (2002). "Structural characterization of the catalytic domain of the human 5-lipoxygenase enzyme." Journal of Molecular Modeling 8(4): 102-112. <http://hdl.handle.net/2027.42/47877>en_US
dc.identifier.issn0948-5023en_US
dc.identifier.issn1610-2940en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/47877
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=12111389&dopt=citationen_US
dc.description.abstractLeukotrienes are inflammatory mediators involved in several diseases. The enzyme 5-lipoxygenase initiates the synthesis of leukotrienes from arachidonic acid. Little structural information is available regarding 5-lipoxygenase. In this study, we found that the primary structure of the catalytic domain of human 5-lipoxygenase is similar to that of the rabbit 15-lipoxygenase. This similarity allowed the development of a theoretical model of the tertiary structure of the 5-lipoxygenase catalytic domain, using the resolved structure of rabbit 15-lipoxygenase as a template. This model was used in conjunction with primary and secondary structural information to investigate putative nucleotide binding sites, a MAPKAP kinase 2 phosphorylation site, and a Src homology 3 binding site on the 5-lipoxygenase protein, further. Results indicate that the putative nucleotide binding sites are spatially distinct, with one on the β-barrel domain and the other(s) on the catalytic domain. The MAPKAP kinase 2 phosphorylation site involves a four amino acid insertion in mammalian 5-lipoxygenases that significantly alters molecular structure. This target for post-translational modification is both common and unique to 5-lipoxygenases. The Src homology 3 binding site, found in all lipoxygenases, appears to lack the characteristic left-handed type II helix structure of known Src homology 3 binding sites. These results, which highlight the unique nature of the MAPKAP kinase site, underscore the utility of structural information in the analysis of protein function. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00894-002-0076-y.en_US
dc.format.extent681251 bytes
dc.format.extent3115 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.language.isoen_US
dc.publisherSpringer-Verlagen_US
dc.subject.otherChemistryen_US
dc.subject.other5-Lipoxygenase – Catalytic Domain – Nucleotide – Kinasesen_US
dc.titleStructural characterization of the catalytic domain of the human 5-lipoxygenase enzymeen_US
dc.typeArticleen_US
dc.subject.hlbsecondlevelMolecular, Cellular, and Developmental Biologyen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, 6301 MSRB III, Ann Arbor, MI 48109–0642, USA. E-mail: brocko@umich.edu Phone: +1-734-7639077 Fax: +1-734-7644556, US,en_US
dc.contributor.affiliationumDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, 6301 MSRB III, Ann Arbor, MI 48109–0642, USA. E-mail: brocko@umich.edu Phone: +1-734-7639077 Fax: +1-734-7644556, US,en_US
dc.contributor.affiliationumDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, 6301 MSRB III, Ann Arbor, MI 48109–0642, USA. E-mail: brocko@umich.edu Phone: +1-734-7639077 Fax: +1-734-7644556, US,en_US
dc.contributor.affiliationumcampusAnn Arboren_US
dc.identifier.pmid12111389en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/47877/1/894_2002_Article_76.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1007/s00894-002-0076-yen_US
dc.identifier.sourceJournal of Molecular Modelingen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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