Abstrakt
RMPK is a homotetramer. Each subunit consists of 530 amino acids and multiple domains.
The active site resides between the A and B domains. Besides the basic TIM-barrel motif, RMPK also exhibits looped-out regions in the α/β barrel of each monomer forming the B- and C-domains.
The two isozymes of PK, namely, the kidney and muscle isozymes, exhibit very different allosteric behaviors under the same experimental condition. The only amino acid sequence differences between the mammalian kidney and muscle PK isozymes are located in the C-domain and are involved in intersubunit interactions.
Thus, embedded in these two isozymes of PK are the rules involved in engineering the popular TIM (α/β)8 motif to modulate its allosteric properties. The PK system exhibits a lot of the properties that will allow mining of the ground rules governing the correlative linkages between sequence-fold-function.
In this chapter, we review the approaches to acquire the fundamental functional and structural energetics that establish the linkages among this intricate network of linked multiequilibria. Results from these diverse approaches are integrated to establish a working model to represent the complex network of multiple linked reactions which ultimately leads to the observation of allosteric regulation of PK.