The role of short hydrogen bonds in mechanisms of enzymatic action

Golubev, N. S.; Денисов, Г. С.; Gindin, V. A.; Ligay, S.S.; Limbach, Hans−Heinrich; Смирнов, С. Н.

doi:10.1016/0022-2860(94)87023-3

Journal of Molecular Structure

1994

DOI: 10.1016/0022-2860(94)87023-3

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The role of short hydrogen bonds in mechanisms of enzymatic action

N. S. Golubev

Г. С. Денисов

V. A. Gindin³

et al.

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Cited by 18 publications

(22 citation statements)

References 14 publications

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“…The mechanism explains the function of the low barrier hydrogen bond (LBHB) between His 57 and Asp 102 (2,3). Chemical, spectroscopic, and X-ray crystallographic evidence indicate that a substrate-induced conformational change introduces steric compression between N ͳ1 of His 57 and the ͱ-carboxyl group of Asp 102.…”

mentioning

confidence: 96%

Steric Enhancement of Imidazole Basicity incis-Urocanic Acid Derivatives: Models for the Action of Chymotrypsin

Cloninger

Frey

1998

Bioorganic Chemistry

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mentioning

confidence: 96%

Steric Enhancement of Imidazole Basicity incis-Urocanic Acid Derivatives: Models for the Action of Chymotrypsin

Cloninger

Frey

1998

Bioorganic Chemistry

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“…[8,9] In particular, it was argued on theoretical grounds [8] that a lowbarrier hydrogen bond that is stable in the gas phase or in the solid state may be unstable in a polar solvent. In this case specific solvation could lead to charge localization and a fast equilibrium between two asymmetric tautomers, [7] that is, A À H´´´B > A À´´´H À B…”

mentioning

confidence: 99%

“…[7] Recently, the concept of transition state stabilization through strong hydrogen bonding has been questioned. [8,9] In particular, it was argued on theoretical grounds [8] that a lowbarrier hydrogen bond that is stable in the gas phase or in the solid state may be unstable in a polar solvent.…”

mentioning

confidence: 99%

Nuclear Scalar Spin-Spin Coupling Reveals Novel Properties of Low-Barrier Hydrogen Bonds in a Polar Environment

et al. 1999

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“…Histidine pairs are observed in a number of proteins, such as myoglobin (40). In ribonuclease, a strong hydrogen bond between two histidine residues has been described (41). Such interactions have been studied by using imidazole and imidazolium, which form cocrystals displaying a strong hydrogen bond (42), and modeling them computationally (43).…”

mentioning

confidence: 99%

Histidines, heart of the hydrogen ion channel from influenza A virus: Toward an understanding of conductance and proton selectivity

Nishimura

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

240

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The heart of the H ؉ conductance mechanism in the homotetrameric M2 H ؉ channel from influenza A is a set of four histidine side chains. Here, we show that protonation of the third of these imidazoles coincides with acid activation of this transmembrane channel and that, at physiological pH, the channel is closed by two imidazole-imidazolium dimers, each sharing a low-barrier hydrogen bond. This unique construct succeeds in distributing a pair of charges over four rings and many atoms in a low dielectric environment to minimize charge repulsion. These dimers form with identical pK as of 8.2 ؎ 0.2, suggesting cooperative H ؉ binding and clearly illustrating high H ؉ affinity for this channel. The protonation behavior of the histidine side chains has been characterized by using solid-state NMR spectroscopy on the M2 transmembrane domain in fully hydrated lipid bilayers where the tetrameric backbone structure is known. Furthermore, electrophysiological measurements of multichannel and single-channel experiments confirm that these protein constructs are functional.M2 channel ͉ proton channel ͉ solid-state NMR ͉ low-barrier hydrogen bond ͉ histidine ionization constants A histidine tetrad in the pore of the tetrameric M2 protein has long been associated with key channel features of H ϩ selectivity, pH activation, gating, inhibition, and the specific conductance mechanism. M2 protein from influenza A virus conducts protons into the viral core after endocytosis, which leads to the uncoating and release of genetic material into the cytoplasm after fusion of the viral coat with the endosomal wall (1, 2). Much is known about this system from its tetrameric state (2-4), the backbone structure of the transmembrane (TM) domain (5), and numerous electrophysiological (6, 7), biophysical (8-10), and modeling (11) studies that have cast a fascinating tale for this important influenza drug target and the only proton channel of its kind to be characterized in such detail. However, the specific role of His-37 in the tetrameric protein has not been elucidated. Here, we have characterized the pK a s associated with this cluster of four histidine residues in the hydrophobic interstices of the membrane. These pK a values have led us to substantial mechanistic conclusions.There are many lines of evidence, reviewed by Kelly et al. (6), that support the conclusion that M2 is responsible for viral acidification. In vivo ion conductance recordings have shown pH sensitive conductance resulting in rapid acidification of the Xenopus oocytes (12, 13) and mammalian cells (13-15) containing M2 protein.Preparations of purified M2 protein have also been used to show proton conductance in synthetic lipid bilayers (16,17). Singlechannel conductance measurements with membranes containing M2 protein give clear evidence that it is H ϩ conductance, not counterion conductance, that is observed. Furthermore, the channel conductance is unchanged by addition of an excess of NaCl (18). Conductance measurements for the isolated TM domain of M2 protein have als...

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The role of short hydrogen bonds in mechanisms of enzymatic action

Cited by 18 publications

References 14 publications

Steric Enhancement of Imidazole Basicity incis-Urocanic Acid Derivatives: Models for the Action of Chymotrypsin

Steric Enhancement of Imidazole Basicity incis-Urocanic Acid Derivatives: Models for the Action of Chymotrypsin

Nuclear Scalar Spin-Spin Coupling Reveals Novel Properties of Low-Barrier Hydrogen Bonds in a Polar Environment

Histidines, heart of the hydrogen ion channel from influenza A virus: Toward an understanding of conductance and proton selectivity

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