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Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.
Hicks, Kevin G; Cluntun, Ahmad A; Schubert, Heidi L; Hackett, Sean R; Berg, Jordan A; Leonard, Paul G; Ajalla Aleixo, Mariana A; Zhou, Youjia; Bott, Alex J; Salvatore, Sonia R; Chang, Fei; Blevins, Aubrie; Barta, Paige; Tilley, Samantha; Leifer, Aaron; Guzman, Andrea; Arok, Ajak; Fogarty, Sarah; Winter, Jacob M; Ahn, Hee-Chul; Allen, Karen N; Block, Samuel; Cardoso, Iara A; Ding, Jianping; Dreveny, Ingrid; Gasper, William C; Ho, Quinn; Matsuura, Atsushi; Palladino, Michael J; Prajapati, Sabin; Sun, Pengkai; Tittmann, Kai; Tolan, Dean R; Unterlass, Judith; VanDemark, Andrew P; Vander Heiden, Matthew G; Webb, Bradley A; Yun, Cai-Hong; Zhao, Pengkai; Wang, Bei; Schopfer, Francisco J; Hill, Christopher P; Nonato, Maria Cristina; Muller, Florian L; Cox, James E; Rutter, Jared.
Affiliation
  • Hicks KG; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Cluntun AA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Schubert HL; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Hackett SR; Calico Life Sciences LLC, South San Francisco, CA, USA.
  • Berg JA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Leonard PG; Core for Biomolecular Structure and Function, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ajalla Aleixo MA; Institute for Applied Cancer Sciences, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zhou Y; Laboratório de Cristalografia de Proteinas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Bott AJ; School of Computing, University of Utah, Salt Lake City, UT, USA.
  • Salvatore SR; Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA.
  • Chang F; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Blevins A; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Barta P; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Tilley S; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Leifer A; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Guzman A; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Arok A; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Fogarty S; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Winter JM; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Ahn HC; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Allen KN; Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Block S; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Cardoso IA; Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, The Republic of Korea.
  • Ding J; Department of Chemistry, Boston University, Boston, MA, USA.
  • Dreveny I; The Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Gasper WC; Laboratório de Cristalografia de Proteinas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Ho Q; State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Shanghai, China.
  • Matsuura A; Biodiscovery Institute, School of Pharmacy, University of Nottingham, Nottingham, UK.
  • Palladino MJ; Department of Biology, Boston University, Boston, MA, USA.
  • Prajapati S; Department of Biology, Boston University, Boston, MA, USA.
  • Sun P; Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, The Republic of Korea.
  • Tittmann K; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Tolan DR; Department of Molecular Enzymology, Göttingen Center of Molecular Biosciences, University of Göttingen, Göttingen, Germany.
  • Unterlass J; Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • VanDemark AP; State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Shanghai, China.
  • Vander Heiden MG; Department of Molecular Enzymology, Göttingen Center of Molecular Biosciences, University of Göttingen, Göttingen, Germany.
  • Webb BA; Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Yun CH; Department of Biology, Boston University, Boston, MA, USA.
  • Zhao P; Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
  • Wang B; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
  • Schopfer FJ; The Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Hill CP; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Nonato MC; Department of Biochemistry, West Virginia University, Morgantown, WV, USA.
  • Muller FL; Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
  • Cox JE; Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
  • Rutter J; School of Computing, University of Utah, Salt Lake City, UT, USA.
Science ; 379(6636): 996-1003, 2023 03 10.
Article in En | MEDLINE | ID: mdl-36893255
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carbohydrate Metabolism / Metabolome / L-Lactate Dehydrogenase Limits: Humans Language: En Journal: Science Year: 2023 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carbohydrate Metabolism / Metabolome / L-Lactate Dehydrogenase Limits: Humans Language: En Journal: Science Year: 2023 Type: Article Affiliation country: United States