CNAD: A potent and specific inhibitor of alcohol dehydrogenase Journal Article

  


Authors: Goldstein, B. M.; Li, H.; Jones, J. P.; Bell, J. E.; Zeidler, J.; Pankiewicz, K. W.; Watanabe, K. A.
Article Title: CNAD: A potent and specific inhibitor of alcohol dehydrogenase
Abstract: CNAD (5-β-D-ribofuranosylnicotinamide adenine dinucleotide) is an isosteric and isomeric analogue of NAD, in which the nicotinamide ring is linked to the sugar via a C-glycosyl (C5-C1 ́) bond. CNAD acts as a general dehydrogenase inhibitor but shows unusual specificity and affinity for liver alcohol dehydrogenase (ADH, EC 1.1.1.1). The pattern of inhibition is competitive, with Ki ≃4 nM, with NAD as the variable substrate. These values are 3–5 orders of magnitude smaller than those obtained for CNAD in other dehydrogenases and are comparable to values observed for the tightest binding ADH inhibitors known. The specificity and affinity of CNAD for ADH are likely due to coordination of the zinc cation at the ADH catalytic site by the CNAD pyridine nitrogen. This is supported by kinetic and computational studies of ADH-CNAD complexes. These results are compared with those for a related analogue, CPAD. In this analogue, displacement of the pyridine nitrogen to the opposite side of the ring removes the specificity for ADH. © 1994, American Chemical Society. All rights reserved.
Keywords: unclassified drug; animal; enzyme inhibition; enzyme inhibitor; drug specificity; liver; kinetics; crystal structure; computer simulation; models, molecular; thermodynamics; binding sites; cattle; molecular structure; structure analysis; enzyme binding; reaction analysis; reduced nicotinamide adenine dinucleotide; nad; nicotinamide adenine dinucleotide; mathematical analysis; horses; competitive inhibition; alcohol dehydrogenase; binding, competitive; article; support, u.s. gov't, p.h.s.; nicotinamide 5 beta riboside adenine dinucleotide
Journal Title: Journal of Medicinal Chemistry
Volume: 37
Issue: 3
ISSN: 0022-2623
Publisher: American Chemical Society  
Date Published: 1994-02-01
Start Page: 392
End Page: 399
Language: English
DOI: 10.1021/jm00029a011
PROVIDER: scopus
PUBMED: 8308865
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028204761&doi=10.1021%2fjm00029a011&partnerID=40&md5=0797a2cec9ad30e5124ca91aec12dde2
Notes: Article -- Source: Scopus
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MSK Authors
  1. Kyoichi A Watanabe
    125 Watanabe
  2. Krzystof W. Pankiewicz
    43 Pankiewicz
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