1lf3: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1lf3.gif|left|200px]] | [[Image:1lf3.gif|left|200px]] | ||
'''CRYSTAL STRUCTURE OF PLASMEPSIN II FROM P FALCIPARUM IN COMPLEX WITH INHIBITOR EH58''' | {{Structure | ||
|PDB= 1lf3 |SIZE=350|CAPTION= <scene name='initialview01'>1lf3</scene>, resolution 2.70Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=EH5:N-(1-BENZYL-3-{[3-(1,3-DIOXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PROPIONYL]-[2-(HEXAHYDRO-BENZO[1,3]DIOXOL-5-YL)-ETHYL]-AMINO}-2-HYDROXY-PROPYL)-4-BENZYLOXY-3,5-DIMETHOXY-BENZAMIDE'>EH5</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Plasmepsin_II Plasmepsin II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.39 3.4.23.39] | |||
|GENE= | |||
}} | |||
'''CRYSTAL STRUCTURE OF PLASMEPSIN II FROM P FALCIPARUM IN COMPLEX WITH INHIBITOR EH58''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1LF3 is a [ | 1LF3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LF3 OCA]. | ||
==Reference== | ==Reference== | ||
Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum., Asojo OA, Gulnik SV, Afonina E, Yu B, Ellman JA, Haque TS, Silva AM, J Mol Biol. 2003 Mar 14;327(1):173-81. PMID:[http:// | Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum., Asojo OA, Gulnik SV, Afonina E, Yu B, Ellman JA, Haque TS, Silva AM, J Mol Biol. 2003 Mar 14;327(1):173-81. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12614616 12614616] | ||
[[Category: Plasmepsin II]] | [[Category: Plasmepsin II]] | ||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
| Line 26: | Line 35: | ||
[[Category: plasmodium falciparum]] | [[Category: plasmodium falciparum]] | ||
''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 12:30:12 2008'' | ||
Revision as of 13:30, 20 March 2008
| |||||||
| , resolution 2.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Plasmepsin II, with EC number 3.4.23.39 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF PLASMEPSIN II FROM P FALCIPARUM IN COMPLEX WITH INHIBITOR EH58
OverviewOverview
Malaria remains a human disease of global significance and a major cause of high infant mortality in endemic nations. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Hemoglobin degradation is initiated by aspartic proteases, termed plasmepsins, with a cleavage at the alpha-chain between residues Phe33 and Leu34. Plasmepsin II is one of the four catalytically active plasmepsins that has been identified in the food vacuole of Plasmodium falciparum. Novel crystal structures of uncomplexed plasmepsin II as well as the complex with a potent inhibitor have been refined with data extending to resolution limits of 1.9A and 2.7A, and to R factors of 17% and 18%, respectively. The inhibitor, N-(3-[(2-benzo[1,3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoind ol-2-yl)-propionyl]-amino]-1-benzyl-2-(hydroxypropyl)-4-benzyloxy-3,5-dime thoxy-benzamide, belongs to a family of potent non-peptidic inhibitors that have large P1' groups. Such inhibitors could not be modeled into the binding cavity of the structure of plasmepsin II in complex with pepstatin A. Our structures reveal that the binding cavities of the new complex and uncomplexed plasmepsin II are considerably more open than that of the pepstatin A complex, allowing for larger heterocyclic groups in the P1', P2' and P2 positions. Both complexed and uncomplexed plasmepsin II crystallized in space group P2, with one monomer in the asymmetric unit. The structures show extensive interlocking of monomers around the crystallographic axis of symmetry, with areas in excess of 2300A(2) buried at the interface, and a loop of one monomer interacting with the binding cavity of the 2-fold related monomer. Electron density for this loop is only fully ordered in the complexed structure.
About this StructureAbout this Structure
1LF3 is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
ReferenceReference
Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum., Asojo OA, Gulnik SV, Afonina E, Yu B, Ellman JA, Haque TS, Silva AM, J Mol Biol. 2003 Mar 14;327(1):173-81. PMID:12614616
Page seeded by OCA on Thu Mar 20 12:30:12 2008