1n2e
From Proteopedia
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| - | [[Image:1n2e.gif|left|200px]] | + | [[Image:1n2e.gif|left|200px]] |
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| - | '''Crystal Structure of a Pantothenate Synthetase from M. tuberculosis in complex with AMPCPP and pantoate''' | + | {{Structure |
| + | |PDB= 1n2e |SIZE=350|CAPTION= <scene name='initialview01'>1n2e</scene>, resolution 1.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=PAF:PANTOATE'>PAF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> and <scene name='pdbligand=EOH:ETHANOL'>EOH</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Pantoate--beta-alanine_ligase Pantoate--beta-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.1 6.3.2.1] | ||
| + | |GENE= panC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of a Pantothenate Synthetase from M. tuberculosis in complex with AMPCPP and pantoate''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1N2E is a [ | + | 1N2E 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=1N2E OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate., Wang S, Eisenberg D, Protein Sci. 2003 May;12(5):1097-108. PMID:[http:// | + | Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate., Wang S, Eisenberg D, Protein Sci. 2003 May;12(5):1097-108. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12717031 12717031] |
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Pantoate--beta-alanine ligase]] | [[Category: Pantoate--beta-alanine ligase]] | ||
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[[Category: psi]] | [[Category: psi]] | ||
[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
| - | [[Category: structural | + | [[Category: structural genomic]] |
[[Category: tb structural genomics consortium]] | [[Category: tb structural genomics consortium]] | ||
[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''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 12:51:14 2008'' |
Revision as of 10:51, 20 March 2008
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| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , and | ||||||
| Gene: | panC (Mycobacterium tuberculosis) | ||||||
| Activity: | Pantoate--beta-alanine ligase, with EC number 6.3.2.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of a Pantothenate Synthetase from M. tuberculosis in complex with AMPCPP and pantoate
Overview
Pantothenate biosynthesis is essential for the virulence of Mycobacterium tuberculosis, and this pathway thus presents potential drug targets against tuberculosis. We determined the crystal structure of pantothenate synthetase (PS) from M. tuberculosis, and its complexes with AMPCPP, pantoate, and a reaction intermediate, pantoyl adenylate, with resolutions from 1.6 to 2 A. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Its structure reveals a dimer, and each subunit has two domains with tight association between domains. The active-site cavity is on the N-terminal domain, partially covered by the C-terminal domain. One wall of the active site cavity is flexible, which allows the bulky AMPCPP to diffuse into the active site to nearly full occupancy when crystals are soaked in solutions containing AMPCPP. Crystal structures of the complexes with AMPCPP and pantoate indicate that the enzyme binds ATP and pantoate tightly in the active site, and brings the carboxyl oxygen of pantoate near the alpha-phosphorus atom of ATP for an in-line nucleophilic attack. When crystals were soaked with, or grown in the presence of, both ATP and pantoate, a reaction intermediate, pantoyl adenylate, is found in the active site. The flexible wall of the active site cavity becomes ordered when the intermediate is in the active site, thus protecting it from being hydrolyzed. Binding of beta-alanine can occur only after pantoyl adenylate is formed inside the active site cavity. The tight binding of the intermediate pantoyl adenylate suggests that nonreactive analogs of pantoyl adenylate may be inhibitors of the PS enzyme with high affinity and specificity.
About this Structure
1N2E is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate., Wang S, Eisenberg D, Protein Sci. 2003 May;12(5):1097-108. PMID:12717031
Page seeded by OCA on Thu Mar 20 12:51:14 2008
Categories: Mycobacterium tuberculosis | Pantoate--beta-alanine ligase | Single protein | Eisenberg, D. | TBSGC, TB Structural Genomics Consortium. | Wang, S. | APC | EOH | GOL | MG | PAF | SO4 | Dimer | Intersubunit beta sheet | Protein structure initiative | Psi | Rossmann fold | Structural genomic | Tb structural genomics consortium | Tbsgc
