View source for 4plh


==Crystal structure of ancestral apicomplexan malate dehydrogenase with oxamate.==
<StructureSection load='4plh' size='340' side='right' caption='[[4plh]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4plh]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PLH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PLH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=OXM:OXAMIC+ACID'>OXM</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4plc|4plc]], [[4plf|4plf]], [[4plg|4plg]], [[4plt|4plt]], [[4plv|4plv]], [[4plw|4plw]], [[4ply|4ply]], [[4plz|4plz]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4plh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4plh OCA], [http://pdbe.org/4plh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4plh RCSB], [http://www.ebi.ac.uk/pdbsum/4plh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4plh ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Malate and lactate dehydrogenases (MDH and LDH) are homologous, core metabolic enzymes that share a fold and catalytic mechanism yet possess strict specificity for their substrates. In the Apicomplexa, convergent evolution of an unusual LDH from MDH resulted in a difference in substrate preference exceeding 12 orders of magnitude. The molecular and evolutionary mechanisms responsible for this extraordinary functional shift are currently unknown. Using ancestral sequence reconstruction, we find that the evolution of pyruvate specificity in apicomplexan LDHs arose through a classic neofunctionalization mechanism characterized by long-range epistasis, a promiscuous intermediate, and relatively few gain-of-function mutations of large effect. Residues far from the active site determine specificity, as shown by the crystal structures of three ancestral proteins that bracket the key gene duplication event. This work provides an unprecedented atomic-resolution view of evolutionary trajectories resulting in the de novo creation of a nascent enzymatic function.

An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases.,Boucher JI, Jacobowitz JR, Beckett BC, Classen S, Theobald DL Elife. 2014 Jun 25:e02304. doi: 10.7554/eLife.02304. PMID:24966208<ref>PMID:24966208</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4plh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Malate dehydrogenase|Malate dehydrogenase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Beckett, B C]]
[[Category: Boucher, J I]]
[[Category: Classen, S]]
[[Category: Jacobowitz, J R]]
[[Category: Theobald, D L]]
[[Category: Ancestral sequence reconstruction]]
[[Category: Apicomplexa]]
[[Category: Dehydrogenase]]
[[Category: Oxidoreductase]]
[[Category: Specificity]]