7LUB

Crystal structure of recombinant human fumarase in complex with D-2-amino-3-phosphono-propionic acid

Summary for 7LUB

• Entry DOI: 10.2210/pdb7lub/pdb
• Descriptor: Fumarate hydratase, mitochondrial, D-2-AMINO-3-PHOSPHONO-PROPIONIC ACID, GLYCEROL, ... (4 entities in total)
• Functional Keywords: fumarase, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 100893.22

Authors

Cardoso, I.A.,Nonato, M.C. (deposition date: 2021-02-21, release date: 2022-02-23, Last modification date: 2023-10-25)

Primary citation

Hicks, K.G.,Cluntun, A.A.,Schubert, H.L.,Hackett, S.R.,Berg, J.A.,Leonard, P.G.,Ajalla Aleixo, M.A.,Zhou, Y.,Bott, A.J.,Salvatore, S.R.,Chang, F.,Blevins, A.,Barta, P.,Tilley, S.,Leifer, A.,Guzman, A.,Arok, A.,Fogarty, S.,Winter, J.M.,Ahn, H.C.,Allen, K.N.,Block, S.,Cardoso, I.A.,Ding, J.,Dreveny, I.,Gasper, W.C.,Ho, Q.,Matsuura, A.,Palladino, M.J.,Prajapati, S.,Sun, P.,Tittmann, K.,Tolan, D.R.,Unterlass, J.,VanDemark, A.P.,Vander Heiden, M.G.,Webb, B.A.,Yun, C.H.,Zhao, P.,Wang, B.,Schopfer, F.J.,Hill, C.P.,Nonato, M.C.,Muller, F.L.,Cox, J.E.,Rutter, J.
Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.
Science, 379:996-1003, 2023

PubMed Abstract: 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.

PubMed: 36893255
DOI: 10.1126/science.abm3452

Experimental method

X-RAY DIFFRACTION (2.15 Å)