View source for 4uuo


==Apo Trichomonas vaginalis malate dehydrogenase==
<StructureSection load='4uuo' size='340' side='right'caption='[[4uuo]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4uuo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trichomonas_vaginalis Trichomonas vaginalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UUO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.842&#8491;</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=4uuo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uuo OCA], [https://pdbe.org/4uuo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uuo RCSB], [https://www.ebi.ac.uk/pdbsum/4uuo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uuo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q27819_TRIVA Q27819_TRIVA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lactate and malate dehydrogenases (LDH and MDH) are homologous, core metabolic enzymes common to nearly all living organisms. LDHs have evolved convergently from MDHs at least four times, achieving altered substrate specificity by a different mechanism each time. For instance, the LDH of anaerobic trichomonad parasites recently evolved independently from an ancestral trichomonad MDH by gene duplication. LDH plays a central role in trichomonad metabolism by catalyzing the reduction of pyruvate to lactate, thereby regenerating the NAD+ required for glycolysis. Using ancestral reconstruction methods, we identified the biochemical and evolutionary mechanisms responsible for this convergent event. The last common ancestor of these enzymes was a highly specific MDH, similar to modern trichomonad MDHs. In contrast, the LDH lineage evolved promiscuous activity by relaxing specificity in a gradual process of neofunctionalization involving one highly detrimental substitution at the "specificity residue" (R91L) and many additional mutations of small effect. L91 has different functional consequences in LDHs and in MDHs, indicating a prominent role for epistasis. Crystal structures of modern-day and ancestral enzymes show that the evolution of substrate specificity paralleled structural changes in dimerization and alpha-helix orientation. The relatively small "specificity residue" of the trichomonad LDHs can accommodate a range of substrate sizes and may permit solvent to access the active site, both of which promote substrate promiscuity. The trichomonad LDHs present a multi-faceted counterpoint to the independent evolution of LDHs in other organisms and illustrate the diverse mechanisms by which protein function, structure, and stability coevolve. This article is protected by copyright. All rights reserved.

Gradual neofunctionalization in the convergent evolution of trichomonad lactate and malate dehydrogenases.,Steindel PA, Chen EH, Wirth JD, Theobald DL Protein Sci. 2016 Feb 17. doi: 10.1002/pro.2904. PMID:26889885<ref>PMID:26889885</ref>

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

==See Also==
*[[Malate Dehydrogenase 3D structures|Malate Dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trichomonas vaginalis]]
[[Category: Chen EH]]
[[Category: Steindel PA]]
[[Category: Theobald DL]]