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Protein & Peptide Letters
ISSN (Print): 0929-8665
ISSN (Online): 1875-5305
VOLUME: 18
ISSUE: 4
DOI: 10.2174/092986611794654003      Price:  $58









Role of Protein Conformational Dynamics in the Catalysis by 6-Hydroxymethyl-7, 8-Dihydropterin Pyrophosphokinase

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Author(s): Honggao Yan and Xinhua Ji
Pages 328-335 (8)
Abstract:
Enzymatic catalysis has conflicting structural requirements of the enzyme. In order for the enzyme to form a Michaelis complex, the enzyme must be in an open conformation so that the substrate can get into its active center. On the other hand, in order to maximize the stabilization of the transition state of the enzymatic reaction, the enzyme must be in a closed conformation to maximize its interactions with the transition state. The conflicting structural requirements can be resolved by a flexible active center that can sample both open and closed conformational states. For a bisubstrate enzyme, the Michaelis complex consists of two substrates in addition to the enzyme. The enzyme must remain flexible upon the binding of the first substrate so that the second substrate can get into the active center. The active center is fully assembled and stabilized only when both substrates bind to the enzyme. However, the side-chain positions of the catalytic residues in the Michaelis complex are still not optimally aligned for the stabilization of the transition state, which lasts only approximately 10-13 s. The instantaneous and optimal alignment of catalytic groups for the transition state stabilization requires a dynamic enzyme, not an enzyme which undergoes a large scale of movements but an enzyme which permits at least a small scale of adjustment of catalytic group positions. This review will summarize the structure, catalytic mechanism, and dynamic properties of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase and examine the role of protein conformational dynamics in the catalysis of a bisubstrate enzymatic reaction.
Keywords:
Bisubstrate enzyme, enzymatic catalysis, folate biosynthesis, 6-hydroxymethyl-7, 8-dihydropterin pyrophosphokinase, HPPK, NMR, protein dynamics, X-ray crystallography, Michaelis complex, ARGININE 82 AND ARGININE 92, apo enzyme, ligand-bound, enzyme-substrate complex, 15N relaxation, de novo, DHNA, DHFS, dihydrofolate reductase, MgATP binding, AMPCPP, fluorometry, PDB code, protein's hydrophobic core., ternary complex, HP analogue, enzymatic catalysi, ARGININE 82 AND ARGININE 93Bisubstrate enzyme, enzymatic catalysis, folate biosynthesis, 6-hydroxymethyl-7, 8-dihydropterin pyrophosphokinase, HPPK, NMR, protein dynamics, X-ray crystallography, Michaelis complex, ARGININE 82 AND ARGININE 92, apo enzyme, ligand-bound, enzyme-substrate complex, 15N relaxation, de novo, DHNA, DHFS, dihydrofolate reductase, MgATP binding, AMPCPP, fluorometry, PDB code, protein's hydrophobic core., ternary complex, HP analogue, enzymatic catalysi, ARGININE 82 AND ARGININE 93
Affiliation:
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.