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Crystal Structures of Pinoresinol-Lariciresinol and Phenylcoumaran Benzylic Ether Reductases and Their Relationship to Isoflavone Reductases

Despite the importance of plant lignans and isoflavonoids in human health protection (e.g. for both treatment and prevention of onset of various cancers) as well as in plant biology (e.g. in defense functions and in heartwood development), systematic studies on the enzymes involved in their biosynth...

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Published in:The Journal of biological chemistry 2003-12, Vol.278 (50), p.50714-50723
Main Authors: Min, Tongpil, Kasahara, Hiroyuki, Bedgar, Diana L., Youn, Buhyun, Lawrence, Paulraj K., Gang, David R., Halls, Steven C., Park, HaJeung, Hilsenbeck, Jacqueline L., Davin, Laurence B., Lewis, Norman G., Kang, ChulHee
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cited_by cdi_FETCH-LOGICAL-c432t-8be820a22dd92dcd4619c723dbb58025626075ea8975269bbbb6398a8850aab13
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creator Min, Tongpil
Kasahara, Hiroyuki
Bedgar, Diana L.
Youn, Buhyun
Lawrence, Paulraj K.
Gang, David R.
Halls, Steven C.
Park, HaJeung
Hilsenbeck, Jacqueline L.
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Lewis, Norman G.
Kang, ChulHee
description Despite the importance of plant lignans and isoflavonoids in human health protection (e.g. for both treatment and prevention of onset of various cancers) as well as in plant biology (e.g. in defense functions and in heartwood development), systematic studies on the enzymes involved in their biosynthesis have only recently begun. In this investigation, three NADPH-dependent aromatic alcohol reductases were comprehensively studied, namely pinoresinol-lariciresinol reductase (PLR), phenylcoumaran benzylic ether reductase (PCBER), and isoflavone reductase (IFR), which are involved in central steps to the various important bioactive lignans and isoflavonoids. Of particular interest was in determining how differing regio- and enantiospecificities are achieved with the different enzymes, despite each apparently going through similar enone intermediates. Initially, the three-dimensional x-ray crystal structures of both PLR_Tp1 and PCBER_Pt1 were solved and refined to 2.5 and 2.2 Å resolutions, respectively. Not only do they share high gene sequence similarity, but their structures are similar, having a continuous α/β NADPH-binding domain and a smaller substrate-binding domain. IFR (whose crystal structure is not yet obtained) was also compared (modeled) with PLR and PCBER and was deduced to have the same overall basic structure. The basis for the distinct enantio-specific and regio-specific reactions of PCBER, PLR, and IFR, as well as the reaction mechanism and participating residues involved (as identified by site-directed mutagenesis), are discussed.
doi_str_mv 10.1074/jbc.M308493200
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source ScienceDirect Journals
subjects Amino Acid Sequence
Crystallography, X-Ray
Escherichia coli - metabolism
Furans
Life Sciences (General)
Lignans - chemistry
Models, Chemical
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
NADP - chemistry
Oxidoreductases - chemistry
Oxidoreductases Acting on CH-CH Group Donors - chemistry
Plasmids - metabolism
Protein Binding
Protein Conformation
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Ultracentrifugation
title Crystal Structures of Pinoresinol-Lariciresinol and Phenylcoumaran Benzylic Ether Reductases and Their Relationship to Isoflavone Reductases
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