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Article: Crystal structure of 3-hydroxyanthranilic acid 3,4-dioxygenase from Saccharomyces cerevisiae: A special subgroup of the type III extradiol dioxygenases

TitleCrystal structure of 3-hydroxyanthranilic acid 3,4-dioxygenase from Saccharomyces cerevisiae: A special subgroup of the type III extradiol dioxygenases
Authors
Keywords2-His-1-carboxylate facial triad
3-hydroxyanthranilic acid 3,4-dioxygenase
Cupin superfamily
Extradiol dioxygenase
Kynurenine pathway
MAD
X-ray crystallography
Issue Date2006
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.proteinscience.org
Citation
Protein Science, 2006, v. 15 n. 4, p. 761-773 How to Cite?
Abstract3-Hydroxyanthranilic acid 3,4-dioxygenase (3HAO) is a non-heme ferrous extradiol dioxygenase in the kynurenine pathway from tryptophan. It catalyzes the conversion of 3-hydroxyanthranilate (HAA) to quinolinic acid (QUIN), an endogenous neurotoxin, via the activation of N-methyl-D-aspartate (NMDA) receptors and the precursor of NAD + biosynthesis. The crystal structure of 3HAO from S. cerevisiae at 2.4 Å resolution shows it to be a member of the functionally diverse cupin superfamily. The structure represents the first eukaryotic 3HAO to be resolved. The enzyme forms homodimers, with two nickel binding sites per molecule. One of the bound nickel atoms occupies the proposed ferrous-coordinated active site, which is located in a conserved double-strand b-helix domain. Examination of the structure reveals the participation of a series of residues in catalysis different from other extradiol dioxygenases. Together with two iron-binding residues (His49 and Glu55), Asp120, Asn51, Glu111, and Arg114 form a hydrogen-bonding network; this hydrogen-bond network is key to the catalysis of 3HAO. Residues Arg101, Gln59, and the substrate-binding hydrophobic pocket are crucial for substrate specificity. Structure comparison with 3HAO from Ralstonia metallidurans reveals similarities at the active site and suggests the same catalytic mechanism in prokaryotic and eukaryotic 3HAO. Based on sequence comparison, we suggest that bicupin of human 3HAO is the first example of evolution from a monocupin dimer to bicupin monomer in the diverse cupin superfamilies. Based on the model of the substrate HAA at the active site of Y3HAO, we propose a mechanism of catalysis for 3HAO. Copyright © 2006 The Protein Society.
Persistent Identifierhttp://hdl.handle.net/10722/91951
ISSN
2015 Impact Factor: 3.039
2015 SCImago Journal Rankings: 2.029
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Xen_HK
dc.contributor.authorGuo, Men_HK
dc.contributor.authorFan, Jen_HK
dc.contributor.authorTang, Wen_HK
dc.contributor.authorWang, Den_HK
dc.contributor.authorGe, Hen_HK
dc.contributor.authorRong, Hen_HK
dc.contributor.authorTeng, Men_HK
dc.contributor.authorNiu, Len_HK
dc.contributor.authorLiu, Qen_HK
dc.contributor.authorHao, Qen_HK
dc.date.accessioned2010-09-17T10:31:29Z-
dc.date.available2010-09-17T10:31:29Z-
dc.date.issued2006en_HK
dc.identifier.citationProtein Science, 2006, v. 15 n. 4, p. 761-773en_HK
dc.identifier.issn0961-8368en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91951-
dc.description.abstract3-Hydroxyanthranilic acid 3,4-dioxygenase (3HAO) is a non-heme ferrous extradiol dioxygenase in the kynurenine pathway from tryptophan. It catalyzes the conversion of 3-hydroxyanthranilate (HAA) to quinolinic acid (QUIN), an endogenous neurotoxin, via the activation of N-methyl-D-aspartate (NMDA) receptors and the precursor of NAD + biosynthesis. The crystal structure of 3HAO from S. cerevisiae at 2.4 Å resolution shows it to be a member of the functionally diverse cupin superfamily. The structure represents the first eukaryotic 3HAO to be resolved. The enzyme forms homodimers, with two nickel binding sites per molecule. One of the bound nickel atoms occupies the proposed ferrous-coordinated active site, which is located in a conserved double-strand b-helix domain. Examination of the structure reveals the participation of a series of residues in catalysis different from other extradiol dioxygenases. Together with two iron-binding residues (His49 and Glu55), Asp120, Asn51, Glu111, and Arg114 form a hydrogen-bonding network; this hydrogen-bond network is key to the catalysis of 3HAO. Residues Arg101, Gln59, and the substrate-binding hydrophobic pocket are crucial for substrate specificity. Structure comparison with 3HAO from Ralstonia metallidurans reveals similarities at the active site and suggests the same catalytic mechanism in prokaryotic and eukaryotic 3HAO. Based on sequence comparison, we suggest that bicupin of human 3HAO is the first example of evolution from a monocupin dimer to bicupin monomer in the diverse cupin superfamilies. Based on the model of the substrate HAA at the active site of Y3HAO, we propose a mechanism of catalysis for 3HAO. Copyright © 2006 The Protein Society.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.proteinscience.orgen_HK
dc.relation.ispartofProtein Scienceen_HK
dc.subject2-His-1-carboxylate facial triaden_HK
dc.subject3-hydroxyanthranilic acid 3,4-dioxygenaseen_HK
dc.subjectCupin superfamilyen_HK
dc.subjectExtradiol dioxygenaseen_HK
dc.subjectKynurenine pathwayen_HK
dc.subjectMADen_HK
dc.subjectX-ray crystallographyen_HK
dc.titleCrystal structure of 3-hydroxyanthranilic acid 3,4-dioxygenase from Saccharomyces cerevisiae: A special subgroup of the type III extradiol dioxygenasesen_HK
dc.typeArticleen_HK
dc.identifier.emailHao, Q: qhao@hku.hken_HK
dc.identifier.authorityHao, Q=rp01332en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1110/ps.051967906en_HK
dc.identifier.pmid16522801-
dc.identifier.pmcidPMC2242480-
dc.identifier.scopuseid_2-s2.0-33645502064en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33645502064&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue4en_HK
dc.identifier.spage761en_HK
dc.identifier.epage773en_HK
dc.identifier.isiWOS:000236734200010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, X=8160498200en_HK
dc.identifier.scopusauthoridGuo, M=34569788700en_HK
dc.identifier.scopusauthoridFan, J=36672761400en_HK
dc.identifier.scopusauthoridTang, W=12799652100en_HK
dc.identifier.scopusauthoridWang, D=8517449000en_HK
dc.identifier.scopusauthoridGe, H=7102931147en_HK
dc.identifier.scopusauthoridRong, H=12799414200en_HK
dc.identifier.scopusauthoridTeng, M=7101891754en_HK
dc.identifier.scopusauthoridNiu, L=7101760477en_HK
dc.identifier.scopusauthoridLiu, Q=35215401600en_HK
dc.identifier.scopusauthoridHao, Q=7102508868en_HK

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