1b5q
A 30 ANGSTROM U-SHAPED CATALYTIC TUNNEL IN THE CRYSTAL STRUCTURE OF POLYAMINE OXIDASE
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| , resolution 1.9Å | |||||||
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| Ligands: | , and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
BACKGROUND: Polyamines are essential for cell growth and differentiation; compounds interfering with their metabolism are potential anticancer agents. Polyamine oxidase (PAO) plays a central role in polyamine homeostasis. The enzyme utilises an FAD cofactor to catalyse the oxidation of the secondary amino groups of spermine and spermidine. RESULTS: The first crystal structure of a polyamine oxidase has been determined to a resolution of 1.9 Angstroms. PAO from Zea mays contains two domains, which define a remarkable 30 Angstrom long U-shaped catalytic tunnel at their interface. The structure of PAO in complex with the inhibitor MDL72527 reveals the residues forming the catalytic machinery and unusual enzyme-inhibitor CH.O H bonds. A ring of glutamate and aspartate residues surrounding one of the two tunnel openings contributes to the steering of the substrate towards the inside of the tunnel. CONCLUSIONS: PAO specifically oxidizes substrates that have both primary and secondary amino groups. The complex with MDL72527 shows that the primary amino groups are essential for the proper alignment of the substrate with respect to the flavin. Conservation of an N-terminal sequence motif indicates that PAO is member of a novel family of flavoenzymes. Among these, monoamine oxidase displays significant sequence homology with PAO, suggesting a similar overall folding topology.
About this StructureAbout this Structure
1B5Q is a Single protein structure of sequence from Zea mays. Full crystallographic information is available from OCA.
ReferenceReference
A 30-angstrom-long U-shaped catalytic tunnel in the crystal structure of polyamine oxidase., Binda C, Coda A, Angelini R, Federico R, Ascenzi P, Mattevi A, Structure. 1999 Mar 15;7(3):265-76. PMID:10368296
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