From Proteopedia
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| - | [[Image:1pzf.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1pzf.png|left|200px]] |
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| | {{STRUCTURE_1pzf| PDB=1pzf | SCENE= }} | | {{STRUCTURE_1pzf| PDB=1pzf | SCENE= }} |
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| - | '''T.gondii LDH1 ternary complex with APAD+ and oxalate'''
| + | ===T.gondii LDH1 ternary complex with APAD+ and oxalate=== |
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| - | ==Overview==
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| - | While within a human host the opportunistic pathogen Toxoplasma gondii relies heavily on glycolysis for its energy needs. Lactate dehydrogenase (LDH), the terminal enzyme in anaerobic glycolysis necessary for NAD(+) regeneration, therefore represents an attractive therapeutic target. The tachyzoite stage lactate dehydrogenase (LDH1) from the parasite T. gondii has been crystallized in apo form and in ternary complexes containing NAD(+) or the NAD(+)-analogue 3-acetylpyridine adenine dinucleotide (APAD(+)) and sulfate or the inhibitor oxalate. Comparison of the apo and ternary models shows an active-site loop that becomes ordered upon substrate binding. This active-site loop is five residues longer than in most LDHs and necessarily adopts a different conformation. While loop isomerization is fully rate-limiting in prototypical LDHs, kinetic data suggest that LDH1's rate is limited by chemical steps. The importance of charge neutralization in ligand binding is supported by the complexes that have been crystallized as well as fluorescence quenching experiments performed with ligands at low and high pH. A methionine that replaces a serine residue and displaces an ordered water molecule often seen in LDH structures provides a structural explanation for reduced substrate inhibition. Superimposition of LDH1 with human muscle- and heart-specific LDH isoforms reveals differences in residues that line the active site that increase LDH1's hydrophobicity. These differences will aid in designing inhibitors specific for LDH1 that may be useful in treating toxoplasmic encephalitis and other complications that arise in immune-compromised individuals.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_14744130}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14744130 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_14744130}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Rossmann fold]] | | [[Category: Rossmann fold]] |
| | [[Category: Tetramer]] | | [[Category: Tetramer]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:40:48 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:28:00 2008'' |
Revision as of 02:28, 29 July 2008
Template:STRUCTURE 1pzf
T.gondii LDH1 ternary complex with APAD+ and oxalate
Template:ABSTRACT PUBMED 14744130
About this Structure
1PZF is a Single protein structure of sequence from Toxoplasma gondii. Full crystallographic information is available from OCA.
Reference
Structure of Toxoplasma gondii LDH1: active-site differences from human lactate dehydrogenases and the structural basis for efficient APAD+ use., Kavanagh KL, Elling RA, Wilson DK, Biochemistry. 2004 Feb 3;43(4):879-89. PMID:14744130
Page seeded by OCA on Tue Jul 29 05:28:00 2008
