1sme
From Proteopedia
(New page: 200px<br /> <applet load="1sme" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sme, resolution 2.70Å" /> '''PLASMEPSIN II, A HE...) |
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| - | [[Image:1sme.gif|left|200px]]<br /> | + | [[Image:1sme.gif|left|200px]]<br /><applet load="1sme" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1sme" size=" | + | |
caption="1sme, resolution 2.70Å" /> | caption="1sme, resolution 2.70Å" /> | ||
'''PLASMEPSIN II, A HEMOGLOBIN-DEGRADING ENZYME FROM PLASMODIUM FALCIPARUM, IN COMPLEX WITH PEPSTATIN A'''<br /> | '''PLASMEPSIN II, A HEMOGLOBIN-DEGRADING ENZYME FROM PLASMODIUM FALCIPARUM, IN COMPLEX WITH PEPSTATIN A'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Plasmodium falciparum is the major causative agent of malaria, a disease | + | Plasmodium falciparum is the major causative agent of malaria, a disease of worldwide importance. Resistance to current drugs such as chloroquine and mefloquine is spreading at an alarming rate, and our antimalarial armamentarium is almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development. We have determined the crystal structure of recombinant plasmepsin II complexed with pepstatin A. This represents the first reported crystal structure of a protein from P. falciparum. The crystals contain molecules in two different conformations, revealing a remarkable degree of interdomain flexibility of the enzyme. The structure was used to design a series of selective low molecular weight compounds that inhibit both plasmepsin II and the growth of P. falciparum in culture. |
==About this Structure== | ==About this Structure== | ||
| - | 1SME is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with IHN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1SME is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=IHN:'>IHN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SME OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Erickson, J | + | [[Category: Erickson, J W.]] |
| - | [[Category: Goldberg, D | + | [[Category: Goldberg, D E.]] |
| - | [[Category: Gulnik, S | + | [[Category: Gulnik, S V.]] |
| - | [[Category: Lee, A | + | [[Category: Lee, A Y.]] |
| - | [[Category: Silva, A | + | [[Category: Silva, A M.]] |
[[Category: IHN]] | [[Category: IHN]] | ||
[[Category: aspartic proteinase]] | [[Category: aspartic proteinase]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:02:59 2008'' |
Revision as of 13:02, 21 February 2008
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PLASMEPSIN II, A HEMOGLOBIN-DEGRADING ENZYME FROM PLASMODIUM FALCIPARUM, IN COMPLEX WITH PEPSTATIN A
Overview
Plasmodium falciparum is the major causative agent of malaria, a disease of worldwide importance. Resistance to current drugs such as chloroquine and mefloquine is spreading at an alarming rate, and our antimalarial armamentarium is almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development. We have determined the crystal structure of recombinant plasmepsin II complexed with pepstatin A. This represents the first reported crystal structure of a protein from P. falciparum. The crystals contain molecules in two different conformations, revealing a remarkable degree of interdomain flexibility of the enzyme. The structure was used to design a series of selective low molecular weight compounds that inhibit both plasmepsin II and the growth of P. falciparum in culture.
About this Structure
1SME is a Single protein structure of sequence from Plasmodium falciparum with as ligand. Active as Plasmepsin II, with EC number 3.4.23.39 Full crystallographic information is available from OCA.
Reference
Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum., Silva AM, Lee AY, Gulnik SV, Maier P, Collins J, Bhat TN, Collins PJ, Cachau RE, Luker KE, Gluzman IY, Francis SE, Oksman A, Goldberg DE, Erickson JW, Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10034-9. PMID:8816746
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