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One Key and Multiple Locks: Substrate Binding in Structures of Tryptophan Dioxygenases and Hydroxylases
Author(s) -
Mammoli Andrea,
Riccio Alessandra,
Bianconi Elisa,
Coletti Alice,
Camaioni Emidio,
Macchiarulo Antonio
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100312
Subject(s) - tryptophan , key (lock) , chemistry , substrate specificity , substrate (aquarium) , stereochemistry , biochemistry , computational biology , biology , amino acid , enzyme , ecology
Since its discovery at the beginning of the past century, the essential nutrient l ‐Tryptophan ( l ‐Trp) and its catabolic pathways have acquired an increasing interest in an ever wider scientific community for their pivotal roles in underlying many important physiological functions and associated pathological conditions. As a consequence, enzymes catalyzing rate limiting steps along l ‐Trp catabolic pathways ‐ including IDO1, TDO, TPH1 and TPH2 ‐ have turned to be interesting drug targets for the design and development of novel therapeutic agents for different disorders such as carcinoid syndrome, cancer and autoimmune diseases. This article provides a fresh comparative overview on the most recent advancements that crystallographic studies, biophysical and computational works have brought on structural aspects and molecular recognition patterns of these enzymes toward l ‐Trp. Finally, a conformational analysis of l ‐Trp is also discussed as part of the molecular recognition process governing the binding of a substrate to its cognate enzymes.