Publications

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:

Sì

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:

November 27, 2022

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. 12 , 2007 , pp. 1291-1324

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