4BNP

3D structure of E. coli Isocitrate Dehydrogenase K100M mutant in complex with isocitrate and magnesium(II)

Summary for 4BNP

• Entry DOI: 10.2210/pdb4bnp/pdb
• Descriptor: ISOCITRATE DEHYDROGENASE [NADP], ISOCITRIC ACID, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase, oxidative beta-decarboxylation
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 1
• Total formula weight: 46124.07

Authors

Miller, S.P.,Goncalves, S.,Matias, P.M.,Dean, A.M. (deposition date: 2013-05-16, release date: 2014-05-21, Last modification date: 2023-12-20)

Primary citation

Miller, S.P.,Goncalves, S.,Matias, P.M.,Dean, A.M.
Evolution of a Transition State: Role of Lys100 in the Active Site of Isocitrate Dehydrogenase.
Chembiochem, 15:1145-, 2014

PubMed Abstract: An active site lysine essential to catalysis in isocitrate dehydrogenase (IDH) is absent from related enzymes. As all family members catalyze the same oxidative β-decarboxylation at the (2R)-malate core common to their substrates, it seems odd that an amino acid essential to one is not found in all. Ordinarily, hydride transfer to a nicotinamide C4 neutralizes the positive charge at N1 directly. In IDH, the negatively charged C4-carboxylate of isocitrate stabilizes the ground state positive charge on the adjacent nicotinamide N1, opposing hydride transfer. The critical lysine is poised to stabilize-and perhaps even protonate-an oxyanion formed on the nicotinamide 3-carboxamide, thereby enabling the hydride to be transferred while the positive charge at N1 is maintained. IDH might catalyze the same overall reaction as other family members, but dehydrogenation proceeds through a distinct, though related, transition state. Partial activation of lysine mutants by K(+) and NH4 (+) represents a throwback to the primordial state of the first promiscuous substrate family member.

PubMed: 24797066
DOI: 10.1002/CBIC.201400040

Experimental method

X-RAY DIFFRACTION (2 Å)