Old yellow enzyme at 2 Å resolution: overall structure, ligand binding, and comparison with related flavoproteins

Fox, Kristin M.; Karplus, P. Andrew

doi:10.1016/s0969-2126(94)00111-1

Cited by 247 publications

(317 citation statements)

References 55 publications

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“…3b). This structural correspondence is also found for nearly all structurally characterized members of the OYE family (data not shown) with the exception of His-188, which is replaced by asparagine in several enzymes (19,20,(25)(26)(27)(28). The corresponding atoms Asn N␦2 and His N␦1 that bind the carbonyl oxygen overlay perfectly, however, indicating a similar effect on substrate activation and positioning.…”

Section: Resultssupporting

confidence: 66%

“…loops have been shown to contribute to ligand binding in enzymes of the OYE family (19,20,25). In conclusion, the structural comparison reveals a pronounced structural conservation of catalytically important amino acids and a high variability of loops that interact with the nonreactive part of the substrates.…”

Section: Resultsmentioning

confidence: 83%

“…2a) (19,20). A short hairpin loop at the N terminus and helix ␣B, which is part of loop L8, ‡ ‡ on the opposite side of the barrel are conserved among proteins of the OYE family.…”

Section: Resultsmentioning

confidence: 99%

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Crystal structure of 12-oxophytodienoate reductase 3 from tomato: Self-inhibition by dimerization

Breithaupt

Kurzbauer

Lilie

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

119

109

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12-Oxophytodienoate reductase (OPR) 3, a homologue of old yellow enzyme (OYE), catalyzes the reduction of 9S,13S-12-oxophytodienoate to the corresponding cyclopentanone, which is subsequently converted to the plant hormone jasmonic acid (JA). JA and JA derivatives, as well as 12-oxophytodienoate and related cyclopentenones, are known to regulate gene expression in plant development and defense. Together with other oxygenated fatty acid derivatives, they form the oxylipin signature in plants, which resembles the pool of prostaglandins in animals. Here, we report the crystal structure of OPR3 from tomato and of two OPR3 mutants. Although the catalytic residues of OPR3 and related OYEs are highly conserved, several characteristic differences can be discerned in the substrate-binding regions, explaining the remarkable substrate stereoselectivity of OPR isozymes. Interestingly, OPR3 crystallized as an extraordinary self-inhibited dimer. Mutagenesis studies and biochemical analysis confirmed a weak dimerization of OPR3 in vitro, which correlated with a loss of enzymatic activity. Based on structural data of OPR3, a putative mechanism for a strong and reversible dimerization of OPR3 in vivo that involves phosphorylation of OPR3 is suggested. This mechanism could contribute to the shaping of the oxylipin signature, which is critical for fine-tuning gene expression in plants.flavoprotein ͉ jasmonic acid biosynthesis ͉ plant defense ͉ oxylipin signature ͉ 12-oxophytodienoic acid F lavoproteins catalyze a wide variety of essential biochemical reactions, including electron transfer, dehydrogenation, and hydroxylation reactions. Old yellow enzyme (OYE), the first flavin-dependent enzyme identified (1), and homologues of OYE from bacteria, yeast, and plants are able to reduce the CAC double bond of ␣,␤-unsaturated carbonyl compounds, an activity that is rather uncommon for flavoenzymes (2, 3). This reaction has been shown to proceed by a ping-pong bi-bi mechanism, during which the FMN cofactor is reduced by NAD(P)H before the substrate is bound and reduced by hydride transfer to the substrate's C ␤ (4). Despite extensive efforts, the physiological substrate has been revealed only for one member of the OYE family, the plant enzyme 12-oxophytodienoate reductase (OPR) 3, which catalyzes one step in the biosynthesis of the plant hormone jasmonic acid (JA) (5, 6). JA and JA derivatives act as signaling compounds in the defense response against herbivores and pathogens and are involved in the regulation of various developmental processes, such as fruit ripening, pollen maturation, and senescence (7,8). JA is synthesized from ␣-linolenic acid, which is oxidized and cyclized, resulting in the cyclopentenone 9S,13S-12-oxophytodienoate (9S,13S-OPDA). OPR3 reduces 9S,13S-OPDA to the corresponding cyclopentanone, which is converted to JA by repeated ␤-oxidation ( Fig. 1) (9). Several OPR isozymes have been identified in plants, including 3 isoforms in Lycopersicon esculentum, 5 in Arabidopsis thaliana, and 13 in Oryza sativa (10, 11). O...

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 83%

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Crystal structure of 12-oxophytodienoate reductase 3 from tomato: Self-inhibition by dimerization

Breithaupt

Kurzbauer

Lilie

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

119

109

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“…Residues that form side-chain hydrogen bonds with FMN, including Thr37, Glu114, Arg243, and Arg348 (OYE1 numbering), are strictly conserved or conservatively substituted, whereas those forming main-chain hydrogen bonds with FMN are generally less conserved (Fox and Karplus 1994) (Fig. 1).…”

Section: Database Comparisons and Sequence Analysismentioning

confidence: 99%

“…In contrast to the cis-hydrogenation performed using transition-metal-based catalysts in organic synthesis, the OYE-catalyzed addition of [H 2 ] proceeds in a trans-manner, with a hydride stereoselectively transferred to C β , and a Tyr residue adding a proton to C α from the opposite side. The asymmetric trans-hydrogenation function makes those enzymes important complementary tools for existing chemical catalysts (Brown et al 2002;Fox and Karplus 1994;Kohli and Massey 1998;Xu et al 1999). The substrate range reported covers conjugated enals, enones, ynones, nitroalkenes, α,β-unsaturated nitriles, β-nitro acrylates, and α,β-unsaturated carboxylic acids with high chemo-, regio-, and stereoselectivity, and the products often serve as versatile synthons in pharmaceutical and fine chemical industries (Bougioukou and Stewart 2008;Stueckler et al 2011;Stuermer et al 2007;Toogood et al 2010Toogood et al , 2012.…”

Section: Introductionmentioning

confidence: 99%

An enoate reductase Achr-OYE4 from Achromobacter sp. JA81: characterization and application in asymmetric bioreduction of C=C bonds

Wang

Pei

2013

Appl Microbiol Biotechnol

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A putative enoate reductase, Achr-OYE4, was mined from the genome of Achromobacter sp. JA81, expressed in Escherichia coli, and was characterized. Sequence analysis and spectral properties indicated that Achr-OYE4 is a typical flavin mononucleotide-dependent protein; it preferred NADH over NADPH as a cofactor. The heterologously expressed protein displayed good activity and excellent stereoselectivity toward some activated alkenes in the presence of NADH, NADPH, or their recycling systems. The glucose dehydrogenase-based recycling system yielded the best results in most cases, with a product yield of up to 99 % and enantiopurity of >99 % ee. Achr-OYE4 is an important addition to the asymmetric reduction reservoir as an "old yellow enzyme" from Achromobacter.

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Enzymes, Enolate Reductases “Old Yellow Enzyme”

Hall

Yanto

Bommarius

2010

Encyclopedia of Industrial Biotechnology

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Reported enoate reductase activity is mostly displayed by enzymes belonging to the “Old Yellow Enzyme” family of flavoproteins. They have received increased interest over the last couple of years due to their huge potential in biocatalysis. These FMN‐containing enzymes catalyze the asymmetric reduction of activated C═C bonds at the expense of a nicotinamide cofactor, producing up to two chiral centers. They are also involved in other reductive processes, such as cleavage of nitrate esters, reduction of aromatic nitro groups, and even reduction of alkynes. Increasing knowledge about this family of biocatalysts together with recent advances in biotechnology render the enoate reductases a tool of choice for industrial applications, as catalyzed reactions are usually chemo‐, regio‐ and stereo‐selective, and the enzymes most importantly display a wide substrate spectrum. With enzymatic reactions and mechanisms being generally clearly understood, the efficient production of a number of enantiopure compounds via recycling of the cofactor is now feasible.

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Old yellow enzyme at 2 Å resolution: overall structure, ligand binding, and comparison with related flavoproteins

Cited by 247 publications

References 55 publications

Crystal structure of 12-oxophytodienoate reductase 3 from tomato: Self-inhibition by dimerization

Crystal structure of 12-oxophytodienoate reductase 3 from tomato: Self-inhibition by dimerization

An enoate reductase Achr-OYE4 from Achromobacter sp. JA81: characterization and application in asymmetric bioreduction of C=C bonds

Enzymes, Enolate Reductases “Old Yellow Enzyme”

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