6ECH
Pyruvate Kinase Isoform L-type with phosphorylated Ser12 (pS12) in complex with FBP
Summary for 6ECH
| Entry DOI | 10.2210/pdb6ech/pdb |
| Related | 6ECK |
| Descriptor | Pyruvate kinase PKLR, CHLORIDE ION, 1,6-di-O-phosphono-beta-D-fructofuranose, ... (11 entities in total) |
| Functional Keywords | pkl, pyruvate kinase, glycolysis, transferase |
| Biological source | Rattus norvegicus (Rat) |
| Total number of polymer chains | 4 |
| Total formula weight | 245832.23 |
| Authors | Padyana, A.,Tong, S. (deposition date: 2018-08-07, release date: 2019-12-04, Last modification date: 2024-10-09) |
| Primary citation | Gassaway, B.M.,Cardone, R.L.,Padyana, A.K.,Petersen, M.C.,Judd, E.T.,Hayes, S.,Tong, S.,Barber, K.W.,Apostolidi, M.,Abulizi, A.,Sheetz, J.B.,Aerni, H.R.,Gross, S.,Kung, C.,Samuel, V.T.,Shulman, G.I.,Kibbey, R.G.,Rinehart, J. Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production. Cell Rep, 29:3394-3404.e9, 2019 Cited by PubMed Abstract: Pyruvate kinase is an important enzyme in glycolysis and a key metabolic control point. We recently observed a pyruvate kinase liver isoform (PKL) phosphorylation site at S113 that correlates with insulin resistance in rats on a 3 day high-fat diet (HFD) and suggests additional control points for PKL activity. However, in contrast to the classical model of PKL regulation, neither authentically phosphorylated PKL at S12 nor S113 alone is sufficient to alter enzyme kinetics or structure. Instead, we show that cyclin-dependent kinases (CDKs) are activated by the HFD and responsible for PKL phosphorylation at position S113 in addition to other targets. These CDKs control PKL nuclear retention, alter cytosolic PKL activity, and ultimately influence glucose production. These results change our view of PKL regulation and highlight a previously unrecognized pathway of hepatic CDK activity and metabolic control points that may be important in insulin resistance and type 2 diabetes. PubMed: 31825824DOI: 10.1016/j.celrep.2019.11.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.19 Å) |
Structure validation
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