View source for 7lub


==Crystal structure of recombinant human fumarase in complex with D-2-amino-3-phosphono-propionic acid==
<StructureSection load='7lub' size='340' side='right'caption='[[7lub]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lub]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LUB 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]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APO:D-2-AMINO-3-PHOSPHONO-PROPIONIC+ACID'>APO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7lub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lub OCA], [https://pdbe.org/7lub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lub RCSB], [https://www.ebi.ac.uk/pdbsum/7lub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lub ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FUMH_HUMAN FUMH_HUMAN] Defects in FH are the cause of fumarase deficiency (FHD) [MIM:[https://omim.org/entry/606812 606812]; also known as fumaricaciduria. FHD is characterized by progressive encephalopathy, developmental delay, hypotonia, cerebral atrophy and lactic and pyruvic acidemia.[:]<ref>PMID:9635293</ref>   Defects in FH are the cause of hereditary leiomyomatosis and renal cell cancer (HLRCC) [MIM:[https://omim.org/entry/150800 150800]. A disorder characterized by predisposition to cutaneous and uterine leiomyomas, and papillary type 2 renal cancer which occurs in about 20% of patients.<ref>PMID:11865300</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FUMH_HUMAN FUMH_HUMAN] Also acts as a tumor suppressor.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to systematically discover. We developed mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) to identify such interactions. Analysis of 33 enzymes from human carbohydrate metabolism identified 830 protein-metabolite interactions, including known regulators, substrates, and products as well as previously unreported interactions. We functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. Cell treatment with fatty acids caused a loss of pyruvate-lactate interconversion dependent on lactate dehydrogenase isoform expression. These protein-metabolite interactions may contribute to the dynamic, tissue-specific metabolic flexibility that enables growth and survival in an ever-changing nutrient environment.

Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.,Hicks KG, Cluntun AA, Schubert HL, Hackett SR, Berg JA, Leonard PG, Ajalla Aleixo MA, Zhou Y, Bott AJ, Salvatore SR, Chang F, Blevins A, Barta P, Tilley S, Leifer A, Guzman A, Arok A, Fogarty S, Winter JM, Ahn HC, Allen KN, Block S, Cardoso IA, Ding J, Dreveny I, Gasper WC, Ho Q, Matsuura A, Palladino MJ, Prajapati S, Sun P, Tittmann K, Tolan DR, Unterlass J, VanDemark AP, Vander Heiden MG, Webb BA, Yun CH, Zhao P, Wang B, Schopfer FJ, Hill CP, Nonato MC, Muller FL, Cox JE, Rutter J Science. 2023 Mar 10;379(6636):996-1003. doi: 10.1126/science.abm3452. Epub 2023 , Mar 9. PMID:36893255<ref>PMID:36893255</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lub" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cardoso IA]]
[[Category: Nonato MC]]