1qpr

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spinqualitylabelsall models 1qpr, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

QUINOLINATE PHOSPHORIBOSYLTRANSFERASE (QAPRTASE) FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH PHTHALATE AND PRPCP

Overview

Background:. Mycobacterium tuberculosis is the single most deadly human, pathogen and is responsible for nearly three million deaths every year., Recent elucidation of the mode of action of isoniazid, a frontline, antimycobacterial drug, suggests that NAD metabolism is extremely critical, for this microorganism. M. tuberculosis depends solely on the de novo, pathway to meet its NAD demand. Quinolinic acid phosphoribosyltransferase, (QAPRTase), a key enzyme in the de novo biosynthesis of NAD, provides an, attractive target for designing novel antitubercular drugs. Results:. The, X-ray crystal structure of the M. tuberculosis QAPRTase apoenzyme has been, determined by multiple isomorphous replacement at 2.4 A resolution., Structures of the enzyme have also been solved in complex with the, substrate quinolinic acid (QA), the inhibitory QA analog phthalic acid, (PA), the product nicotinate mononucleotide (NAMN), and as a ternary, complex with PA and a substrate analog, 5-phosphoribosyl-1-(beta-methylene)pyrophosphate (PRPCP). The structure of, the nonproductive QAPRTase-PA-PRPCP Michaelis complex reveals a, 5-phosphoribosyl-1-pyrophosphate-binding site that is different from the, one observed in type I phosphoribosyltransferases (PRTases). The type II, PRTase active site of QAPRTase undergoes conformational changes that, appear to be important in determining substrate specificity and eliciting, productive catalysis. Conclusions:. QAPRTase is the only known, representative of the type II PRTase fold, an unusual alpha/beta barrel, and appears to represent convergent evolution for PRTase catalysis. The, active site of type II PRTase bears little resemblance to the better known, type I enzymes.

About this Structure

1QPR is a Single protein structure of sequence from Mycobacterium tuberculosis with MN, PHT and PPC as ligands. Active as Nicotinate-nucleotide diphosphorylase (carboxylating), with EC number 2.4.2.19 Full crystallographic information is available from OCA.

Reference

Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target., Sharma V, Grubmeyer C, Sacchettini JC, Structure. 1998 Dec 15;6(12):1587-99. PMID:9862811

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