Modification of pK values caused by change in H-bond geometry.

Scheiner, Steve; Hillenbrand, Eric A.

doi:10.1073/pnas.82.9.2741

Cited by 61 publications

(31 citation statements)

References 24 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The second is a result of the effect ofthe isomerization process itself on the energy of the retinal system (25). A change in the hydrogen-bonding geometry (26) around the PSB (27) or the H-bond strength (44) could also lead to further reduction in its pKa value. During the K61 -L550 transformation, the retinal system and its environment change further and this could lead to further reduction in the PKa of the PSB.…”

Section: Resultsmentioning

confidence: 99%

“…This reduction in the pKa has been attributed to a change in the electrostatic interaction with the anions (23,24), isomerization (25), a change in the hydrogen-bonding geometry around the PSB (26,27), and a cation-PSB electrostatic repulsion during the L550 --M412 step (28). Experimentally, the rate of the L550 --M412 step is found to be determined by the rate of the protein conformational change (28) and not by the rate of the proton dissociation (22).…”

mentioning

confidence: 96%

See 1 more Smart Citation

On the molecular mechanisms of the Schiff base deprotonation during the bacteriorhodopsin photocycle

Chronister

Corcoran

et al. 1986

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

View full text Add to dashboard Cite

Using optical flash photolysis and timeresolved Raman methods, we examined intermediates formed during the photocycle of bacteriorhodopsin (bR), as well as the bR color change, as a function of pH (in the 7.0-1.5 region) and as a function of the number of bound Ca2+ ions. It is found that at a pH just below 3 or with less than two bound Ca21 per bR, the deprotonation (the L550 -_ M412) step ceases, yet the K610 and L550 analogues are still formed as in native bR. The lack of deprotonation in the photocycle of both acid blue and deionized blue bR and the similarity of their Raman spectra as well as of their K610 and L550 analogues strongly suggest that both blue samples have nearly the same retinal active site. It is suggested that in both blue species, bound cations are removed via a proton-cation exchange equilibrium, either on the cation exchange column for the deionized sample or in solution for the acid blue sample. The proton-cation exchange equilibrium is found to quantitatively account for the pH dependence of the purple-to-blue color change. The different mechanisms responsible for the large reduction (=11 units) of the pKa value of the protonated Schiff base (PSB) during the photocycle are discussed. The absence of the L550 1M412 deprotonation process in both blue species is discussed in terms of the previously proposed cation model for the deprotonation of the PSB during the photocycle of native bR. The extent of the deprotonation and the blue-to-purple color change are found to follow the same dependence on either the pH or the amount of cations added to deionized blue bR. This observed correlation is briefly discussed.Bacteriorhodopsin (bR) is the only protein found in the purple membrane of Halabacterium halobium, a light-harvesting bacterium. It contains retinal as a chromophore, which is covalently bound via a protonated Schiff base linkage to the E-amino group of a lysine residue in the protein (1, 2). Upon absorbing a photon, it undergoes a photochemical cycle (3) The photocycle causes protons to be pumped across the cell membrane to the outside, establishing a pH gradient used by the organism for metabolic processes such as ATP synthesis (4-7). The protons are ejected from the cell at a rate comparable to that for the formation of the M412 intermediate (8,9). A good correlation has been found between the number ofprotons pumped and the amount of slow decaying (10) form of M412. This intermediate is the only one in which the Schiff base is unprotonated (11-16). Consequently, many studies have inferred that the protonated Schiff base (PSB) deprotonation is closely associated with the proton pump mechanism (17). Preceding M412 formation (or PSB deprotonation) is the formation of the early intermediates K610 and L550. The retinal in bR570 is in the all-trans form, while in K610 it has a distorted 13-cis conformation (18)(19)(20). In the L550 form, the isomerization is complete (18-20).The pKa value of the PSB is 13.3 in bR570 (21, 22), yet it deprotonates during the cycle, suggesting a lar...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 96%

On the molecular mechanisms of the Schiff base deprotonation during the bacteriorhodopsin photocycle

Chronister

Corcoran

et al. 1986

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

View full text Add to dashboard Cite

show abstract

“…First, hydrogen bond strength is very sensitive to geometry [17,21] and geometry may not be optimized. Second, solvent polarizability decreases hydrogen bond strength, which is dominated by electrostatics [17].…”

Section: How Strong Can Hydrogen Bonds Be?mentioning

confidence: 99%

Membrane protein folding: how important are hydrogen bonds?

Bowie

2011

Current Opinion in Structural Biology

150

141

View full text Add to dashboard Cite

Water is an inhospitable environment for protein hydrogen bonds because it is polarizable and capable of forming competitive hydrogen bonds. In contrast, the apolar core of a biological membrane seems like an ideal environment for hydrogen bonds, and it has long been assumed that hydrogen bonding should be a powerful force driving membrane protein folding. Nevertheless, while backbone hydrogen bonds may be much stronger in membrane proteins, experimental measurements indicate that side chain hydrogen bond strengths are not strikingly different in membrane and water soluble proteins. How is this possible? I argue that that model compounds in apolar solvents do not adequately describe the system because the protein itself is ignored. The protein chain provides a rich source of competitive hydrogen bonds and a polarizable environment that can weaken hydrogen bonds. Thus, just like water soluble proteins, evolution can drive the creation of potent hydrogen bonds in membrane proteins where necessary, but mitigating forces in their environment must still be overcome.Many residues in the hydrocarbon-spanning region of membrane proteins are polar [1] and they are often engaged in hydrogen bonding interactions between transmembrane helices. Indeed almost all transmembrane helices have at least one interhelical hydrogen bond [2]. There is no doubt that hydrogen bonding interactions can play key roles in structure stabilization [3][4][5][6][7] [8,9]. Polar side chains are likely sites of disease causing mutations [10] and mutations to polar side chains can lead to inappropriate interactions that cause disease [11][12][13][14][15]. Nevertheless, quantitative measures of hydrogen bond strengths to date suggest that the stabilization afforded by side chain hydrogen bonds is usually not much different than is seen in water soluble proteins. Moreover, the fraction of apparently unsatisfied hydrogen bond donors and acceptors is similar in both classes of proteins [16]. As discussed here, many factors can reduce hydrogen bond strength in membrane proteins. How strong can hydrogen bonds be?The energy of an amide hydrogen bond in vacuo is arguably the upper limit of its free energy since the entropic contribution is presumably unfavorable and anything more polarizable than a vacuum will reduce the contribution of the electrostatic interactions [17]. Quantum mechanical calculations of amide hydrogen bond strengths using a formamideformaledehyde model suggest that an amide hydrogen bond has an in vacuo energy of 6.6 kcal/mol [17]. Calculations for an N-methylacetamide dimer also agree that the energy of the hydrogen bond in a vacuum is about 6.6 kcal/mol [18]. Experimentally determined vapor © 2010 Elsevier Ltd. All rights reserved.Address: Boyer Hall, UCLA, 611 Charles E. Young Dr. E., Los Angeles, CA 90095-1570, bowie@mbi.ucla.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. T...

show abstract

“…We have chosen the 4-31G* basis set for everything except the evalua-tion of the electrostatic potential surface; this basis set has been used successfully in other studies. 20 The electrostatic potential energy surface used for fitting partial charges was obtained with a 6-31G* basis set, whose suitability for such applications has been established by Carlson et al 21 …”

Section: Vmentioning

confidence: 99%

A potential function for computer simulation studies of proton transfer in acetylacetone

Hinsen

Roux

1997

J. Comput. Chem.

View full text Add to dashboard Cite

A potential energy model is developed to study the intramolecular proton transfer in the enol form of acetylacetone. It makes use of the empirical valence bond approach developed by Warshel to combine standard molecular mechanics potentials for the reactant and product states to reproduce the interconversion between these two states. Most parameters have been fitted to reproduce the key features of an ab initio potential surface obtained from 4‐31G* Hartree‐Fock calculations. The partial charges have been fitted to reproduce the electrostatic potential surface of 6‐31G* Hartree‐Fock wave functions, subject to total charge and symmetry constraints, using a fitting procedure based on generalized inverses. The resulting potential energy function reproduces the features most important for proton transfer simulations, while being several orders of magnitude faster in evaluation time than ab initio energy calculations. © 1997 by John Wiley & Sons, Inc.

show abstract

Modification of pK values caused by change in H-bond geometry.

Cited by 61 publications

References 24 publications

On the molecular mechanisms of the Schiff base deprotonation during the bacteriorhodopsin photocycle

On the molecular mechanisms of the Schiff base deprotonation during the bacteriorhodopsin photocycle

Membrane protein folding: how important are hydrogen bonds?

A potential function for computer simulation studies of proton transfer in acetylacetone

Contact Info

Product

Resources

About