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1v8b

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{{STRUCTURE_1v8b| PDB=1v8b | SCENE= }}
{{STRUCTURE_1v8b| PDB=1v8b | SCENE= }}
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'''Crystal structure of a hydrolase'''
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===Crystal structure of a hydrolase===
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==Overview==
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The human malaria parasite Plasmodium falciparum is responsible for the death of more than a million people each year. The emergence of strains of malarial parasite resistant to conventional drug therapy has stimulated searches for antimalarials with novel modes of action. S-Adenosyl-L-homocysteine hydrolase (SAHH) is a regulator of biological methylations. Inhibitors of SAHH affect the methylation status of nucleic acids, proteins, and small molecules. P.falciparum SAHH (PfSAHH) inhibitors are expected to provide a new type of chemotherapeutic agent against malaria. Despite the pressing need to develop selective PfSAHH inhibitors as therapeutic drugs, only the mammalian SAHH structures are currently available. Here, we report the crystal structure of PfSAHH complexed with the reaction product adenosine (Ado). Knowledge of the structure of the Ado complex in combination with a structural comparison with Homo sapiens SAHH (HsSAHH) revealed that a single substitution between the PfSAHH (Cys59) and HsSAHH (Thr60) accounts for the differential interactions with nucleoside inhibitors. To examine roles of the Cys59 in the interactions with nucleoside inhibitors, a mutant PfSAHH was prepared. A replacement of Cys59 by Thr results in mutant PfSAHH, which shows HsSAHH-like nucleoside inhibitor sensitivity. The present structure should provide opportunities to design potent and selective PfSAHH inhibitors.
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(as it appears on PubMed at http://www.pubmed.gov), where 15476817 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15476817}}
==About this Structure==
==About this Structure==
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[[Category: Tanaka, N.]]
[[Category: Tanaka, N.]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:12:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:16:48 2008''

Revision as of 08:16, 28 July 2008

Image:1v8b.png

Template:STRUCTURE 1v8b

Crystal structure of a hydrolase

Template:ABSTRACT PUBMED 15476817

About this Structure

1V8B is a Single protein structure of sequence from Plasmodium falciparum 3d7. Full crystallographic information is available from OCA.

Reference

Crystal structure of S-adenosyl-L-homocysteine hydrolase from the human malaria parasite Plasmodium falciparum., Tanaka N, Nakanishi M, Kusakabe Y, Shiraiwa K, Yabe S, Ito Y, Kitade Y, Nakamura KT, J Mol Biol. 2004 Oct 29;343(4):1007-17. PMID:15476817

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