PMID- 21195229
OWN - NLM
STAT- MEDLINE
DCOM- 20110517
LR  - 20131121
IS  - 1557-7988 (Electronic)
IS  - 0076-6879 (Linking)
VI  - 488
DP  - 2011
TI  - Structural and functional energetic linkages in allosteric regulation of muscle 
      pyruvate kinase.
PG  - 185-217
LID - 10.1016/B978-0-12-381268-1.00008-2 [doi]
AB  - The understanding of the molecular mechanisms of allostery in rabbit muscle 
      pyruvate kinase (RMPK) is still in its infancy. Although, there is a paucity of 
      knowledge on the ground rules on how its functions are regulated, RMPK is an 
      ideal system to address basic questions regarding the fundamental chemical 
      principles governing the regulatory mechanisms about this enzyme which has a TIM 
      (alpha/beta)(8) barrel structural motif [Copley, R. R., and Bork, P. (2000). Homology 
      among (betaalpha)8 barrels: Implications for the evolution of metabolic pathways. J. 
      Mol. Biol.303, 627-640; Farber, G. K., and Petsko, G. A. (1990). The evolution of 
      alpha/ss barrel enzymes. Trends Biochem.15, 228-234; Gerlt, J. A., and Babbitt, P. C. 
      (2001). Divergent evolution of enzymatic function: Mechanistically diverse 
      superfamilies and functionally distinct superfamilies. Annu. Rev. Biochem.70, 
      209-246; Heggi, H., and Gerstein, M. (1999). The relationship between protein 
      structure and function: A comprehensive survey with application to the yeast 
      genome. J. Mol. Biol.288, 147-164; Wierenga, R. K. (2001). The TIM-barrel fold: A 
      versatile framework for efficient enzymes. FEB Lett.492, 193-198]. 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 alpha/beta 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 (alpha/beta)(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.
CI  - Copyright A(c) 2011 Elsevier Inc. All rights reserved.
FAU - Lee, J Ching
AU  - Lee JC
AD  - Department of Biochemistry and Molecular Biology, The University of Texas Medical 
      Branch at Galveston, Galveston, Texas, USA.
FAU - Herman, Petr
AU  - Herman P
LA  - eng
GR  - GM 77551/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Methods Enzymol
JT  - Methods in enzymology
JID - 0212271
RN  - 0 (Ligands)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 73-89-2 (Phosphoenolpyruvate)
RN  - EC 2.7.1.40 (Pyruvate Kinase)
SB  - IM
MH  - Adenosine Diphosphate/*metabolism
MH  - Allosteric Regulation
MH  - Animals
MH  - Ligands
MH  - Muscles/*enzymology
MH  - Phenylalanine/*metabolism
MH  - Phosphoenolpyruvate/*metabolism
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - Protein Structure, Quaternary
MH  - Protein Structure, Tertiary
MH  - Pyruvate Kinase/chemistry/*metabolism
MH  - Rabbits
MH  - Spectroscopy, Fourier Transform Infrared
MH  - Structure-Activity Relationship
MH  - Thermodynamics
EDAT- 2011/01/05 06:00
MHDA- 2011/05/18 06:00
CRDT- 2011/01/04 06:00
PHST- 2011/01/04 06:00 [entrez]
PHST- 2011/01/05 06:00 [pubmed]
PHST- 2011/05/18 06:00 [medline]
AID - B978-0-12-381268-1.00008-2 [pii]
AID - 10.1016/B978-0-12-381268-1.00008-2 [doi]
PST - ppublish
SO  - Methods Enzymol. 2011;488:185-217. doi: 10.1016/B978-0-12-381268-1.00008-2.