User:Natalya Boufan/Sandbox 1
From Proteopedia
(Difference between revisions)
m |
m |
||
Line 15: | Line 15: | ||
= Function = | = Function = | ||
AceK monitors general metabolism by responding to the levels of a wide variety of metabolites. This ability of AceK allows the IDH phosphorylation cycle to compensate for substantial perturbations of the system. When a less preferred carbon source is available, the cell responds by phosphorylating IDH, thus inactivating IDH and activating the glyoxylate bypass. Many of the regulatory effectors are derived from the end products of the glyoxylate bypass, and represent negative feedback inhibition mechanisms. | AceK monitors general metabolism by responding to the levels of a wide variety of metabolites. This ability of AceK allows the IDH phosphorylation cycle to compensate for substantial perturbations of the system. When a less preferred carbon source is available, the cell responds by phosphorylating IDH, thus inactivating IDH and activating the glyoxylate bypass. Many of the regulatory effectors are derived from the end products of the glyoxylate bypass, and represent negative feedback inhibition mechanisms. | ||
+ | |||
Furthermore, Depletion in AMP levels signals that the cell requires energy and isocitrate will continue through the Krebs cycle with IDH dephosphorylated. AMP binds directly to AceK, activate IDH phosphatase and inhibit both IDH kinase and the intrinsic ATPase activities. An AMP-mediated conformational change exposes and shields ATP, acting as a switch between AceK kinase and phosphatase activities, and ICDH-binding induces further conformational change for AceK activation. During the activation SRL of the kinase domain recognizes the ICDH active cleft and inserts into a binding pocket formed by the ICDH dimer, yielding strict substrate specificity and triggering substrate conformational change for catalysis which allow the Ser113 residue be more accessible for AceK. | Furthermore, Depletion in AMP levels signals that the cell requires energy and isocitrate will continue through the Krebs cycle with IDH dephosphorylated. AMP binds directly to AceK, activate IDH phosphatase and inhibit both IDH kinase and the intrinsic ATPase activities. An AMP-mediated conformational change exposes and shields ATP, acting as a switch between AceK kinase and phosphatase activities, and ICDH-binding induces further conformational change for AceK activation. During the activation SRL of the kinase domain recognizes the ICDH active cleft and inserts into a binding pocket formed by the ICDH dimer, yielding strict substrate specificity and triggering substrate conformational change for catalysis which allow the Ser113 residue be more accessible for AceK. | ||
Revision as of 15:33, 19 March 2018
Isocitrate dehydrogenase kinase/phosphatase
|
References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644