Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis. Academic Article

abstract

• The N-1-(5'-phosphoribosyl)-ATP transferase catalyzes the first step of the histidine biosynthetic pathway and is regulated by a feedback mechanism by the product histidine. The crystal structures of the N-1-(5'-phosphoribosyl)-ATP transferase from Mycobacterium tuberculosis in complex with inhibitor histidine and AMP has been determined to 1.8 A resolution and without ligands to 2.7 A resolution. The active enzyme exists primarily as a dimer, and the histidine-inhibited form is a hexamer. The structure represents a new fold for a phosphoribosyltransferase, consisting of three continuous domains. The inhibitor AMP binds in the active site cavity formed between the two catalytic domains. A model for the mechanism of allosteric inhibition has been derived from conformational differences between the AMP:His-bound and apo structures.

authors

• Sacchettini, James

published proceedings

• J Biol Chem

altmetric score

• 6

author list (cited authors)

• Cho, Y., Sharma, V., & Sacchettini, J. C.

citation count

• 78

complete list of authors

• Cho, Yoonsang||Sharma, Vivek||Sacchettini, James C

publication date

• March 2003

publisher

• Elsevier  Publisher

keywords

• Adenosine Monophosphate
• Atp Phosphoribosyltransferase
• Catalytic Domain
• Cloning, Molecular
• Models, Molecular
• Mycobacterium Tuberculosis
• Protein Structure, Quaternary

Digital Object Identifier (DOI)

• 10.1074/jbc.M212124200

start page

• 8333

end page

• 8339

volume

• 278

issue

• 10

URL

• http://dx.doi.org/10.1074/jbc.m212124200