High impact information on PDK3

• The two swapped C-terminal tails promote conformational changes in active-site clefts of both PDK3 subunits, resulting in largely disordered ATP lids in the ADP-bound form [1].
• PDH2 was found to be very similar to PDH1 as follows: (i) in specific activities and kinetic parameters as determined by the pyruvate dehydrogenase complex assay; (ii) in thermostability at 37 degrees C; (iii) in the mechanism of inactivation by phosphorylation of three sites; and (iv) in the phosphorylation of sites 1 and 2 by PDK3 [2].
• In the present study, we report that alanine substitutions of Leu-140, Glu-170, and Glu-179 in L2 markedly reduce binding affinities of these L2 mutants for PDK3 [3].
• The maximum activation by dihydrolipoamide acetyltransferase was demonstrated by PDK3 [4].
• PDK3 was activated 17-fold by E2; the majority of this activation was facilitated by the free L2 domain (half-maximal activation at 3.3 microm L2) [5].

Anatomical context of PDK3

• In contrast to PDk1 and PDK2, which are expressed in all tissues tested, the message for PDK3 was found almost exclusively in heart and skeletal muscle, indicating that PDK3 may serve specialized functions characteristic of muscle tissues [6].

Associations of PDK3 with chemical compounds

• PDK3 was poorly inhibited by pyruvate or dichloroacetate (DCA) [5].

Other interactions of PDK3

• In contrast, L2 caused a 3-fold increase in PDK3 activity and approx. 37% increase in PDK4 activity [7].
• By using human components, we have evaluated how binding to the lipoyl domains of the dihydrolipoyl acetyltransferase (E2) produces the predominant changes in the rates of phosphorylation of the pyruvate dehydrogenase (E1) component by PDK2 and PDK3 [5].

Analytical, diagnostic and therapeutic context of PDK3

• PDK3 demonstrated a very tight binding, which persisted during isolation of PDK3-L2 complexes using size-exclusion chromatography [7].

References