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PDBsum entry 5mlh
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Oxidoreductase
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PDB id
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5mlh
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References listed in PDB file
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Key reference
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Title
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A multisubstrate reductase from plantago major: structure-Function in the short chain reductase superfamily.
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Authors
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R.Fellows,
C.M.Russo,
C.S.Silva,
S.G.Lee,
J.M.Jez,
J.D.Chisholm,
C.Zubieta,
M.H.Nanao.
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Ref.
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Sci Rep, 2018,
8,
14796.
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PubMed id
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Abstract
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The short chain dehydrogenase/reductase superfamily (SDR) is a large family of
NAD(P)H-dependent enzymes found in all kingdoms of life. SDRs are particularly
well-represented in plants, playing diverse roles in both primary and secondary
metabolism. In addition, some plant SDRs are also able to catalyse a reductive
cyclisation reaction critical for the biosynthesis of the iridoid backbone that
contains a fused 5 and 6-membered ring scaffold. Mining the EST database of
Plantago major, a medicinal plant that makes iridoids, we identified a putative
5β-progesterone reductase gene, PmMOR (P. major multisubstrate
oxido-reductase), that is 60% identical to the iridoid synthase gene from
Catharanthus roseus. The PmMOR protein was recombinantly expressed and its
enzymatic activity assayed against three putative substrates, 8-oxogeranial,
citral and progesterone. The enzyme demonstrated promiscuous enzymatic activity
and was able to not only reduce progesterone and citral, but also to catalyse
the reductive cyclisation of 8-oxogeranial. The crystal structures of PmMOR wild
type and PmMOR mutants in complex with NADP+ or NAD+ and
either 8-oxogeranial, citral or progesterone help to reveal the substrate
specificity determinants and catalytic machinery of the protein. Site-directed
mutagenesis studies were performed and provide a foundation for understanding
the promiscuous activity of the enzyme.
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