2iid
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Structure of L-amino acid oxidase from Calloselasma rhodostoma in complex with L-phenylalanine
OverviewOverview
L-Amino acid oxidase is a dimeric glycosylated flavoenzyme, a major, constituent of the venom-from the snake Calloselasma rhodostoma. The, enzyme exhibits apoptosis inducing effects as well as antibacterial and, anti-HIV activities. The structure of l-amino acid oxidase with its, substrate (L-phenylalanine) has been refined to a resolution of 1.8 A. The, complex structure reveals the substrate bound to the reduced flavin, (FADred). Alternative conformations for the key residues His223 and Arg322, are evident, suggesting a dynamic active site. Furthermore, conformational, changes are apparent for the isoalloxazine ring; the three-ring system, exhibits more bending around the N5-N10 axis compared to the oxidized, flavin. The implications of the observed dynamics on the mechanism of, catalysis are discussed. Inspection of buried surfaces in the enzyme, reveals a Y-shaped channel system extending from the external surface of, the protein to the active site. One portion of this channel may serve as, the entry path for O2 during the oxidative half-reaction. The second, region, separated from the proposed O2 channel by the N terminus (residues, 8-16) of the protein, may play a role in H2O2 release. Interestingly, the, latter portion of the channel would direct the H2O2 product to the, exterior surface of the protein, near the glycan moiety, thought to anchor, the enzyme to the host cell. This channel location may explain the ability, of the enzyme to localize H2O2 to the targeted cell and thus induce the, apoptotic effect.
About this StructureAbout this Structure
2IID is a Single protein structure of sequence from Calloselasma rhodostoma with NAG, PHE and FAD as ligands. Active as L-amino-acid oxidase, with EC number 1.4.3.2 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of LAAO from Calloselasma rhodostoma with an L-phenylalanine substrate: insights into structure and mechanism., Moustafa IM, Foster S, Lyubimov AY, Vrielink A, J Mol Biol. 2006 Dec 15;364(5):991-1002. Epub 2006 Sep 16. PMID:17046020
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