7R6Y

E117K mutant pyruvate kinase from rabbit muscle

Summary for 7R6Y

• Entry DOI: 10.2210/pdb7r6y/pdb
• Descriptor: Pyruvate kinase PKM, ACETATE ION, OXALATE ION, ... (5 entities in total)
• Functional Keywords: mutant, magnesium, oxalate, pyruvate kinase, pk, transferase
• Biological source: Oryctolagus cuniculus (Rabbit)
• Total number of polymer chains: 4
• Total formula weight: 233501.00

Authors

Rodriguez-Romero, A.,Rodriguez-Hernandez, A. (deposition date: 2021-06-24, release date: 2022-05-25, Last modification date: 2023-10-18)

Primary citation

Ramirez-Silva, L.,Hernandez-Alcantara, G.,Guerrero-Mendiola, C.,Gonzalez-Andrade, M.,Rodriguez-Romero, A.,Rodriguez-Hernandez, A.,Lugo-Munguia, A.,Gomez-Coronado, P.A.,Rodriguez-Mendez, C.,Vega-Segura, A.
The K + -Dependent and -Independent Pyruvate Kinases Acquire the Active Conformation by Different Mechanisms.
Int J Mol Sci, 23:-, 2022

PubMed Abstract: Eukarya pyruvate kinases possess glutamate at position 117 (numbering of rabbit muscle enzyme), whereas bacteria have either glutamate or lysine. Those with E117 are K-dependent, whereas those with K117 are K-independent. In a phylogenetic tree, 80% of the sequences with E117 are occupied by T113/K114/T120 and 77% of those with K117 possess L113/Q114/(L,I,V)120. This work aims to understand these residues' contribution to the K-independent pyruvate kinases using the K-dependent rabbit muscle enzyme. Residues 117 and 120 are crucial in the differences between the K-dependent and -independent mutants. K-independent activity increased with L113 and Q114 to K117, but L120 induced structural differences that inactivated the enzyme. T120 appears to be key in folding the protein and closure of the lid of the active site to acquire its active conformation in the K-dependent enzymes. E117K mutant was K-independent and the enzyme acquired the active conformation by a different mechanism. In the K-independent apoenzyme of , K72 (K117) flips out of the active site; in the holoenzyme, K72 faces toward the active site bridging the substrates through water molecules. The results provide evidence that two different mechanisms have evolved for the catalysis of this reaction.

PubMed: 35163274
DOI: 10.3390/ijms23031347

Experimental method

X-RAY DIFFRACTION (2.25 Å)