Autor: Frömmel, J.; Šebela, M.; Demo G.; Lenobel, R.; Pospíšil, T.; Soural, M.; Kopečný, D.
Název práce v češtině: N-acyl-ω-aminoaldehydy jsou účinnými substráty rostlinných aminoaldehyd dehydrogenázových izoenzymů v Pisum sativum
Název práce v angličtině: N-acyl-ω-aminoaldehydes are efficient substrates of plant aminoaldehyde dehydrogenases isoenzymes from Pisum sativum
Studentská publikace: ne
Klíčová slova v češtině: N-acylace; aminoaldehyd dehydrogenázy; isoenzym; KF-celit; NAD+; dockování substrátu
Klíčová slova v angličtině: N-acylation; aminoaldehyde dehydrogenase; isoenzyme; KF-celite; NAD+; substrate docking
Abstrakt česky: Rostlinné aminoaldehyd-ehydrogenázy (AMADHs) tvoří skupinu deseti aldehyd dehydrogenáz účastnících se metabolismu sloučenin příbuzných aminokyselinám jako jsou polyaminy nebo osmoprotektiva. V této práci bylo připraveno 15 nových N-acyl derivátů 3-aminopropanalu a 4-aminobutanalu a tyto sloučeniny byly potvrzeny jako substráty dvou AMADH izoenzymů obsažených v hrachu.
Abstrakt anglicky: Plant aminoaldehyde dehydrogenases (AMADHs, EC 1.2.1.19) constitute the family 10 of aldehyde dehydrogenases and participate in the metabolism of compounds related to amino acids such as polyamines or osmoprotectants. Their broad specificity covers ω-aminoaldehydes, aliphatic and aromatic aldehydes as well as nitrogen-containing heterocyclic aldehydes. The substrate preference of plant AMADHs is determined by the presence of aspartic acid and aromatic residues in the substrate channel. In this work, 15 new N-acyl derivates of 3-aminopropanal (APAL) and 4-aminobutanal (ABAL) were synthesized and confirmed as substrates of two pea AMADH isoenzymes (PsAMADH 1 and 2). The compounds were designed considering the previously demonstrated conversion of N-acetyl derivatives as well as substrate channel dimensions (5-8 Å x 14 Å). The acyl chain length and its branching were found less significant for substrate properties than the length of the initial natural substrate. In general, APAL derivatives were found more efficient than the corresponding ABAL derivatives because of the prevailing higher conversion rates and lower Km values. Differences in enzymatic performance between the two isoenzymes corresponded in part to their preferences to APAL to ABAL. The higher PsAMADH2 affinity to substrates correlated with more frequent occurrence of an excess substrate inhibition. Molecular docking indicated the possible auxiliary role of Tyr163, Ser295 and Gln451 in binding of the new substrates. The only derivative carrying a free carboxyl group (N-adipoyl APAL) was surprisingly better substrate than ABAL in PsAMADH2 reaction indicating that also negatively charged aldehydes might be good substrates for ALDH10 family.
Jazyk v originále: angličtina
Název časopisu: Amino Acids
Rok: 2015
Svazek (ročník): 47
Číslo časopisu v rámci uvedeného svazku: 1
Strana od-do: 175-187

Q1: ne

ISSN časopisu: ISSN: 0939-4451 (Print) 1438-2199 (Online)
Vydavatel: Springer
Způsob financování: LO1204, P501/11/1591, LM2010005