Nucleophile and borate reactivity with nicotinamide adenine dinucleotide and its analogs

Johnson, Sharon L.; Smith, Katrina

doi:10.1021/jo00435a010

Cited by 9 publications

(2 citation statements)

References 14 publications

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“…Reduction of NAD + to yield NADH generates the well-known absorbance at 340 nm and an analogous absorbance occurs after hydride addition to NaAD (Figure S3A,B). It is also established that thiols and a variety of nucleophiles including tris(alkyl)phosphine reductants can reversibly add to C4 of the pyridinium ring of nicotinamides to generate similar absorbances. − Thus, we reasoned that a Cys221-pyridine adduct (intermediates 1 and 2, Figure ) would also be observed by UV–vis spectroscopy if formed at sufficient abundance. Indeed, we demonstrated that an absorbance with a maximum near 370 nm is generated when NAD + was titrated into the WT or S127A forms of LarB, with all solutions argon purged to prevent carboxylation (Figure S3C,D).…”

Section: Resultsmentioning

confidence: 97%

Structure of the LarB–Substrate Complex and Identification of a Reaction Intermediate during Nickel-Pincer Nucleotide Cofactor Biosynthesis

Chatterjee,

Nevarez,

Rankin

et al. 2023

Biochemistry

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LarB catalyzes the first step of biosynthesis for the nickel-pincer nucleotide cofactor by converting nicotinic acid adenine dinucleotide (NaAD) to AMP and pyridinium-3,5-biscarboxylic acid mononucleotide (P2CMN). Prior studies had shown that LarB uses CO2 for substrate carboxylation and reported the structure of a Lactiplantibacillus plantarum LarB·NAD+ complex, revealing a covalent linkage between Cys221 and C4 of the pyridine ring. This interaction was proposed to promote C5 carboxylation, with C5-carboxylated-NaAD suggested to activate magnesium-bound water, leading to phosphoanhydride hydrolysis. Here, we extended the analysis of wild-type LarB by using ultraviolet–visible spectroscopy to obtain additional evidence for cysteinyl side chain attachment to the ring of NAD+, thus demonstrating that this linkage is not a crystallization artifact. Using the S127A variant of L. plantarum LarB, a form of the enzyme with a reduced rate of NaAD hydrolysis, we examined its interaction with the authentic substrate. The intermediate arising from C5 carboxylation of NaAD, dinicotinic acid adenine dinucleotide (DaAD), was identified by using mass spectrometry. S127A LarB exhibited spectroscopic evidence of a Cys221-NAD+ adduct, but a covalent enzyme-NaAD linkage was not detectable. We determined the S127A LarB·NaAD structure, providing new insights into the enzyme mechanism, and tentatively identified the position and mode of CO2 binding. The crystal structure revealed the location of the side chain for Glu180, which was previously disordered, but showed that it is not well positioned to abstract the C5 proton in the adduct species to restore aromaticity as Cys221 is expelled. Based on these combined results, we propose a revised catalytic mechanism of LarB..

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Section: Resultsmentioning

confidence: 97%

Structure of the LarB–Substrate Complex and Identification of a Reaction Intermediate during Nickel-Pincer Nucleotide Cofactor Biosynthesis

Chatterjee,

Nevarez,

Rankin

et al. 2023

Biochemistry

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“…NAD(P) + were shown, by NMR or deuterium exchange, to be also attacked by nucleophilic reagents at C-4, producing 1,4-dihydropyridine. Examples of such reagents are pyruvate [52], thioglycolate [53], cyanide [32], sulfite [54], and phosphate [55]. Other nucleophiles adding to NAD(P) + are hydrazine, hydroxylamine, thiols, enols, imidazole, and borate [32].…”

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confidence: 99%

Redox Enzymes Used in Chiral Syntheses Coupled to Coenzyme Regeneration

Leonida¹

2001

CMC

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Due to their ability to perform reactions in a stereo- and regiospecific manner, while functioning under mild conditions of temperature and pH, enzymes are increasingly used for chiral synthesis in the pharmaceutical industry, in medicinal chemistry, agriculture, cosmetic and food industry. The oxidoreductases as catalysts require a coenzyme (cofactor) which functions as an electron carrier. If used in stoichiometric amounts the cost of coenzymes makes synthetic applications of redox enzymes prohibitively expensive for industrial applications. The present review updates previous discussions about the objectives of cofactor regeneration as a requirement for the applicability of enzymatic redox reactions, and about the strategies customarily used to this end. Different types of chiral syntheses coupled successfully to coenzyme regeneration (amino acid synthesis, lactone synthesis, synthetic reactions involving alcohols, hydroxy acid and steroid synthesis, deracemization) are then discussed. New catalysts, cross-linked enzyme crystals, prepared from redox enzyme are presented in a small paragraph together with some of their applications. Special attention is given to whole cells used in this type of synthesis and their advantages and disadvantages are presented in one paragraph. Finally, different reactors, within which were conducted chiral syntheses catalyzed by oxireductases and coupled to cofactor regeneration, are briefly discussed.

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ChemInform Abstract: NUCLEOPHILE AND BORATE REACTIVITY WITH NICOTINAMIDE ADENINE DINUCLEOTIDE AND ITS ANALOGS

Johnson¹,

Smith²

1977

Chemischer Informationsdienst

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Nucleophile and borate reactivity with nicotinamide adenine dinucleotide and its analogs

Cited by 9 publications

References 14 publications

Structure of the LarB–Substrate Complex and Identification of a Reaction Intermediate during Nickel-Pincer Nucleotide Cofactor Biosynthesis

Structure of the LarB–Substrate Complex and Identification of a Reaction Intermediate during Nickel-Pincer Nucleotide Cofactor Biosynthesis

Redox Enzymes Used in Chiral Syntheses Coupled to Coenzyme Regeneration

ChemInform Abstract: NUCLEOPHILE AND BORATE REACTIVITY WITH NICOTINAMIDE ADENINE DINUCLEOTIDE AND ITS ANALOGS

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