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1onf

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{{STRUCTURE_1onf| PDB=1onf | SCENE= }}
{{STRUCTURE_1onf| PDB=1onf | SCENE= }}
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'''Crystal structure of Plasmodium falciparum Glutathione reductase'''
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===Crystal structure of Plasmodium falciparum Glutathione reductase===
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==Overview==
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The malarial parasite Plasmodium falciparum is known to be sensitive to oxidative stress, and thus the antioxidant enzyme glutathione reductase (GR; NADPH+GSSG+H(+) &lt;==&gt; NADP(+)+2 GSH) has become an attractive drug target for antimalarial drug development. Here, we report the 2.6A resolution crystal structure of P.falciparum GR. The homodimeric flavoenzyme is compared to the related human GR with focus on structural aspects relevant for drug design. The most pronounced differences between the two enzymes concern the shape and electrostatics of a large (450A(3)) cavity at the dimer interface. This cavity binds numerous non-competitive inhibitors and is a target for selective drug design. A 34-residue insertion specific for the GRs of malarial parasites shows no density, implying that it is disordered. The precise location of this insertion along the sequence allows us to explain the deleterious effects of a mutant in this region and suggests new functional studies. To complement the structural comparisons, we report the relative susceptibility of human and plasmodial GRs to a series of tricyclic inhibitors as well as to peptides designed to interfere with protein folding and dimerization. Enzyme-kinetic studies on GRs from chloroquine-resistant and chloroquine-sensitive parasite strains were performed and indicate that the structure reported here represents GR of P.falciparum strains in general and thus is a highly relevant target for drug development.
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(as it appears on PubMed at http://www.pubmed.gov), where 12729762 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12729762}}
==About this Structure==
==About this Structure==
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[[Category: Schirmer, R H.]]
[[Category: Schirmer, R H.]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:03:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:30:34 2008''

Revision as of 10:30, 28 July 2008

Image:1onf.png

Template:STRUCTURE 1onf

Crystal structure of Plasmodium falciparum Glutathione reductase

Template:ABSTRACT PUBMED 12729762

About this Structure

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

Reference

Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development., Sarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, Karplus PA, J Mol Biol. 2003 May 9;328(4):893-907. PMID:12729762

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