Structural basis of substrate-binding specificity of human arylamine N-acetyltransferases

Hong Wu, Ludmila Dombrovsky, Wolfram Tempel, Fernando Martin, Peter Loppnau, Geoffrey H. Goodfellow, Denis M. Grant, Alexander N. Plotnikov

Research output: Contribution to journalArticlepeer-review

115 Scopus citations


The human arylamine N-acetyltransferases NAT1 and NAT2 play an important role in the biotransformation of a plethora of aromatic amine and hydrazine drugs. They are also able to participate in the bioactivation of several known carcinogens. Each of these enzymes is genetically variable in human populations, and polymorphisms in NAT genes have been associated with various cancers. Here we have solved the high resolution crystal structures of human NAT1 and NAT2, including NAT1 in complex with the irreversible inhibitor 2-bromoacetanilide, a NAT1 active site mutant, and NAT2 in complex with CoA, and have refined them to 1.7-, 1.8-, and 1.9-Å resolution, respectively. The crystal structures reveal novel structural features unique to human NATs and provide insights into the structural basis of the substrate specificity and genetic polymorphism of these enzymes.

Original languageEnglish
Pages (from-to)30189-30197
Number of pages9
JournalJournal of Biological Chemistry
Issue number41
StatePublished - 12 Oct 2007
Externally publishedYes


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