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[[Image:1pzf.gif|left|200px]]


{{Structure
==T.gondii LDH1 ternary complex with APAD+ and oxalate==
|PDB= 1pzf |SIZE=350|CAPTION= <scene name='initialview01'>1pzf</scene>, resolution 2.2&Aring;
<StructureSection load='1pzf' size='340' side='right'caption='[[1pzf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene> and <scene name='pdbligand=A3D:3-ACETYLPYRIDINE ADENINE DINUCLEOTIDE'>A3D</scene>
<table><tr><td colspan='2'>[[1pzf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PZF FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
|GENE= lactate dehydrogenase ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 Toxoplasma gondii])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A3D:3-ACETYLPYRIDINE+ADENINE+DINUCLEOTIDE'>A3D</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pzf OCA], [https://pdbe.org/1pzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pzf RCSB], [https://www.ebi.ac.uk/pdbsum/1pzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pzf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/P90613_TOXGO P90613_TOXGO]  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pz/1pzf_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pzf ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


'''T.gondii LDH1 ternary complex with APAD+ and oxalate'''
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<ref>PMID:14744130</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1pzf" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1PZF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PZF OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Large Structures]]
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:[http://www.ncbi.nlm.nih.gov/pubmed/14744130 14744130]
[[Category: L-lactate dehydrogenase]]
[[Category: Single protein]]
[[Category: Toxoplasma gondii]]
[[Category: Toxoplasma gondii]]
[[Category: Elling, R A.]]
[[Category: Elling RA]]
[[Category: Kavanagh, K L.]]
[[Category: Kavanagh KL]]
[[Category: Wilson, D K.]]
[[Category: Wilson DK]]
[[Category: A3D]]
[[Category: OXL]]
[[Category: apad]]
[[Category: apicomplexa]]
[[Category: rossmann fold]]
[[Category: tetramer]]
 
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