Publications

Pyridoxal 5’-Phosphate Enzymes as Targets for Therapeutic Agents  (2007)

Authors:
Amadasi, A; Bertoldi, M; Contestabile, R; Bettati, S; Cellini, B; di Salvo, Ml; Borri-Voltattorni, C; Bossa, F; Mozzarelli, A.
Title:
Pyridoxal 5’-Phosphate Enzymes as Targets for Therapeutic Agents
Year:
2007
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Language:
Inglese
Format:
A Stampa
Referee:
Name of journal:
Current Medicinal Chemistry
ISSN of journal:
0929-8673
N° Volume:
14
Number or Folder:
12
:
Bentham Science Publishers
Page numbers:
1291-1324
Keyword:
vitamin B6-enzymes; drug design; pyridoxal 5'-phosphate; inhibitors; functional genomics
Short description of contents:
The vitamin B6-derived pyridoxal 5’-phosphate (PLP) is the cofactor of enzymes catalyzing a large variety ofchemical reactions mainly involved in amino acid metabolism. These enzymes have been divided in five families and fold typeson the basis of evolutionary relationships and protein structural organization. Almost 1.5% of all genes in prokaryotes code forPLP-dependent enzymes, whereas the percentage is substantially lower in eukaryotes. Although about 4% of enzyme-catalyzedreactions catalogued by the Enzyme Commission are PLP-dependent, only a few enzymes are targets of approved drugs andabout twenty are recognised as potential targets for drugs or herbicides. PLP-dependent enzymes for which there are alreadycommercially available drugs are DOPA decarboxylase (involved in the Parkinson disease), GABA aminotransferase (epilepsy),serine hydroxymethyltransferase (tumors and malaria), ornithine decarboxylase (African sleeping sickness and, potentially,tumors), alanine racemase (antibacterial agents), and human cytosolic branched-chain aminotransferase (pathological statesassociated to the GABA/glutamate equilibrium concentrations). Within each family or metabolic pathway, the enzymes for whichdrugs have been already approved for clinical use are discussed first, reporting the enzyme structure, the catalytic mechanism,the mechanism of enzyme inactivation or modulation by substrate-like or transition state-like drugs, and on-going research forincreasing specificity and decreasing side-effects. Then, PLP-dependent enzymes that have been recently characterized andproposed as drug targets are reported. Finally, the relevance of recent genomic analysis of PLP-dependent enzymes for theselection of drug targets is discussed.
Web page:
https://doi.org/10.2174/092986707780597899
Product ID:
37624
Handle IRIS:
11562/308398
Deposited On:
March 29, 2012
Last Modified:
August 10, 2020
Bibliographic citation:
Amadasi, A; Bertoldi, M; Contestabile, R; Bettati, S; Cellini, B; di Salvo, Ml; Borri-Voltattorni, C; Bossa, F; Mozzarelli, A., Pyridoxal 5’-Phosphate Enzymes as Targets for Therapeutic Agents «Current Medicinal Chemistry» , vol. 14 , n. 122007pp. 1291-1324

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