The low-barrier hydrogen bond in enzymic

Cleland WW, Frey PA, Gerlt JA. The low barrier hydrogen bond in enzymic catalysis. J Biol Chem. 1998 273 25529-25532. 

Mildvan, A.S., Harris, T.K., and Abeygunawardana C. (1999) Nuclear magnetic resonance methods for the detection and study of low-barrier hydrogen bonds on enzymes, in Schramm, V. L. and Purich, D. L. (eds.), Methods in Enzymology, 308, Enzyme Kinetics and Mechanism, Part E, Academic Press, San Diego, pp. 219-247. 

Many studies have looked for low-barrier hydrogen bonds at enzyme active sites, with decidedly mixed results thus far. Currently, the question still remains as to whether LBHBs are important in many systems or are just a novelty associated with specialized hydrogen bonds in the gas phase. Stay tuned ... 

B. Schwartz and D.G. Drucckhammer, A simple method for determining the relative strengths of normal and low-barrier hydrogen bonds in solution Implications to enzyme catalysis, J. Am. Chem. Soc., 117 (1995) 11902. 

The topologically defined region(s) on an enzyme responsible for the binding of substrate(s), coenzymes, metal ions, and protons that directly participate in the chemical transformation catalyzed by an enzyme, ribo-zyme, or catalytic antibody. Active sites need not be part of the same protein subunit, and covalently bound intermediates may interact with several regions on different subunits of a multisubunit enzyme complex. See Lambda (A) Isomers of Metal Ion-Nucleotide Complexes Lock and Key Model of Enzyme Action Low-Barrier Hydrogen Bonds Role in Catalysis Yaga-Ozav /a Plot Yonetani-Theorell Plot Induced-Fit Model Allosteric Interaction... 

The topic of low-barrier hydrogen bonds (LBHBs) and the question of how they are involved in enzyme function has been discussed heavily in the literature recently. Hydrogen bonds between two bases of nearly matched proton affinity often exhibit strongly perturbed bond lengths and spectroscopic parameters it remains somewhat unclear exactly how the spectroscopic parameters reflect total energy or reactivity. In this study, we report H NMR chemical shift data and surveys of structural preferences for the well-studied 0-H---0 systems, and also for less studied, but biologically important N-H-0 systems, in particular the imidazole and imidazolium functionality. The H shifts also show interesting trends in comparison with O-H-O motifs, which will require further scrutiny. 

Hydrogen bonds appear to be essential in all enzyme-catalyzed reactions, although why they are essential and how they promote function is an open question. In recent years a specific hypothesis for their involvement in catalysis has emerged so-called low-barrier hydrogen bonds (LBHB) have been proposed to lower the transition state energy for many enzymatic reactions, including those of serine protease, citrate... 

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