Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis.
J Biol Chem
; 278(10): 8333-9, 2003 Mar 07.
Article
in En
| MEDLINE
| ID: mdl-12511575
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 AMPHis-bound and apo structures.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
ATP Phosphoribosyltransferase
/
Mycobacterium tuberculosis
Language:
En
Journal:
J Biol Chem
Year:
2003
Document type:
Article
Affiliation country:
United States