A DFT study on the microscopic ionization of cysteine in water

Canle, Moisés; Ramos, Daniel R.; Santaballa, J. Arturo

doi:10.1016/j.cplett.2005.09.086

Cited by 19 publications

(20 citation statements)

References 13 publications

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“…26,27,29,[95][96][97][98] The sulfur Kedge XAS spectrum of the cysteine zwitterion reported here is identical to those reported previously, 27,42 apart from calibration differences. However, this work presents the first evidence that the sulfur of aqueous cysteine maintains a durable solvation shell consisting of at least one hydrogen-bonded water molecule.…”

Section: Discussionsupporting

confidence: 71%

The x-ray absorption spectroscopy model of solvation about sulfur in aqueous L-cysteine

Sarangi

Frank

Benfatto

et al. 2012

The Journal of Chemical Physics

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The environment of sulfur in dissolved aqueous L-cysteine has been examined using K-edge x-ray absorption spectroscopy (XAS), extended continuum multiple scattering (ECMS) theory, and density functional theory (DFT). For the first time, bound-state and continuum transitions representing the entire XAS spectrum of L-cysteine sulfur are accurately reproduced by theory. Sulfur K-edge absorption features at 2473.3 eV and 2474.2 eV represent transitions to LUMOs that are mixtures of S-C and S-H σ * orbitals significantly delocalized over the entire L-cysteine molecule. Continuum features at 2479, 2489, and 2530 eV were successfully reproduced using extended continuum theory. The full L-cysteine sulfur K-edge XAS spectrum could not be reproduced without addition of a water-sulfur hydrogen bond. Density functional theory analysis shows that although the Cys(H)S· · · H-OH hydrogen bond is weak (∼2 kcal) the atomic charge on sulfur is significantly affected by this water. MXAN analysis of hydrogen-bonding structures for L-cysteine and water yielded a best fit model featuring a tandem of two water molecules, 2.9 Å and 5.8 Å from sulfur. The model included a S cys · · · H-O w1 H hydrogen-bond of 2.19 Å and of 2.16 Å for H 2 O w1 · · · H-O w2 H. One hydrogen-bonding water-sulfur interaction alone was insufficient to fully describe the continuum XAS spectrum. However, density functional theoretical results are convincing that the water-sulfur interaction is weak and should be only transient in water solution. The durable water-sulfur hydrogen bond in aqueous L-cysteine reported here therefore represents a break with theoretical studies indicating its absence. Reconciling the apparent disparity between theory and result remains the continuing challenge.

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Section: Discussionsupporting

confidence: 71%

The x-ray absorption spectroscopy model of solvation about sulfur in aqueous L-cysteine

Sarangi

Frank

Benfatto

et al. 2012

The Journal of Chemical Physics

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“…1.5 is difficult [2]. Another commonly encountered problem is the ascription of microscopic ionization constants to the measured macroscopic pK a s [1,3]. Therefore, computational determination of absolute or relative pK a s has been receiving considerable attention in recent years [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, computational determination of absolute or relative pK a s has been receiving considerable attention in recent years [4][5][6][7]. Although their accuracy is generally expected to be at most 2 pK a units [7], they already proved useful in discovering the microscopic ionization mechanism of aqueous cysteine [3] and serotonin [8].…”

Section: Introductionmentioning

confidence: 99%

“…However, it usually fails to provide reliable pK a values for more complex systems, like polyprotic acids, very strong or weak acids, or zwitterionic molecules [3,4,8,13]. Significant improvement may be achieved by explicit consideration of several solvent molecules around the ionisable group of the solute.…”

Section: Introductionmentioning

confidence: 99%

“…Several other models that include the solvent molecules explicitly have been proposed [7]. To date, such approaches were successfully applied in calculations of pK a s of simple [4,7] and polyprotic [13] acids, ionisation constants of biological zwitterionic molecules [3,8] and in the investigation of reaction pathways in aqueous solutions [15,16].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Theoretical pKa prediction of O-phosphoserine in aqueous solution

Śmiechowski¹

2010

Chemical Physics Letters

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On the Dynamical Behavior of the Cysteine Dioxygenase‐l‐Cysteine Complex in the Presence of Free Dioxygen and l‐Cysteine

Pietra¹

2017

Chemistry & Biodiversity

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In this work, viable models of cysteine dioxygenase (CDO) and its complex with l-cysteine dianion were built for the first time, under strict adherence to the crystal structure from X-ray diffraction studies, for all atom molecular dynamics (MD). Based on the CHARMM36 FF, the active site, featuring an octahedral dummy Fe(II) model, allowed us observing water exchange, which would have escaped attention with the more popular bonded models. Free dioxygen (O ) and l-cysteine, added at the active site, could be observed being expelled toward the solvating medium under Random Accelerated Molecular Dynamics (RAMD) along major and minor pathways. Correspondingly, free dioxygen (O ), added to the solvating medium, could be observed to follow the same above pathways in getting to the active site under unbiased MD. For the bulky l-cysteine, 600 ns of trajectory were insufficient for protein penetration, and the molecule was stuck at the protein borders. These models pave the way to free energy studies of ligand associations, devised to better clarify how this cardinal enzyme behaves in human metabolism.

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A DFT study on the microscopic ionization of cysteine in water

Cited by 19 publications

References 13 publications

The x-ray absorption spectroscopy model of solvation about sulfur in aqueous L-cysteine

The x-ray absorption spectroscopy model of solvation about sulfur in aqueous L-cysteine

Theoretical pKa prediction of O-phosphoserine in aqueous solution

On the Dynamical Behavior of the Cysteine Dioxygenase‐l‐Cysteine Complex in the Presence of Free Dioxygen and l‐Cysteine

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