1qpq
From Proteopedia
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| - | [[Image:1qpq.gif|left|200px]] | + | [[Image:1qpq.gif|left|200px]] |
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| - | '''Structure of Quinolinic Acid Phosphoribosyltransferase from Mycobacterium Tuberculosis: A Potential TB Drug Target''' | + | {{Structure |
| + | |PDB= 1qpq |SIZE=350|CAPTION= <scene name='initialview01'>1qpq</scene>, resolution 2.45Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=NTM:QUINOLINIC ACID'>NTM</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Nicotinate-nucleotide_diphosphorylase_(carboxylating) Nicotinate-nucleotide diphosphorylase (carboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.19 2.4.2.19] | ||
| + | |GENE= NADC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of Quinolinic Acid Phosphoribosyltransferase from Mycobacterium Tuberculosis: A Potential TB Drug Target''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1QPQ is a [ | + | 1QPQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QPQ OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/9862811 9862811] |
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Nicotinate-nucleotide diphosphorylase (carboxylating)]] | [[Category: Nicotinate-nucleotide diphosphorylase (carboxylating)]] | ||
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[[Category: psi]] | [[Category: psi]] | ||
[[Category: quinolinic acid]] | [[Category: quinolinic acid]] | ||
| - | [[Category: structural | + | [[Category: structural genomic]] |
[[Category: tb structural genomics consortium]] | [[Category: tb structural genomics consortium]] | ||
[[Category: tbsgc]] | [[Category: tbsgc]] | ||
[[Category: type ii prtase]] | [[Category: type ii prtase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:41:00 2008'' |
Revision as of 11:41, 20 March 2008
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| , resolution 2.45Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | NADC (Mycobacterium tuberculosis) | ||||||
| Activity: | Nicotinate-nucleotide diphosphorylase (carboxylating), with EC number 2.4.2.19 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Quinolinic Acid Phosphoribosyltransferase from Mycobacterium Tuberculosis: A Potential TB Drug Target
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
1QPQ is a Single protein structure of sequence from Mycobacterium tuberculosis. 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
Page seeded by OCA on Thu Mar 20 13:41:00 2008
Categories: Mycobacterium tuberculosis | Nicotinate-nucleotide diphosphorylase (carboxylating) | Single protein | Grubmeyer, C. | Sacchettini, J C. | Sharma, V. | TBSGC, TB Structural Genomics Consortium. | NTM | SO4 | De novo nad biosynthesis | Phosphoribosyl transferase | Protein structure initiative | Prpp | Psi | Quinolinic acid | Structural genomic | Tb structural genomics consortium | Tbsgc | Type ii prtase
