Serine Molecules Research Articles

Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages.

Ewing sarcoma (EWS) is the second most common pediatric bone tumor. The EWS tumor microenvironment is largely recognized as immune-cold, with macrophages being the most abundant immune cells and their presence associated with worse patient prognosis. Expression of CD99 is a hallmark of EWS cells, and its targeting induces inhibition of EWS tumor growth through a poorly understood mechanism. In this study, we analyzed CD99 expression and functions on macrophages and investigated whether the concomitant targeting of CD99 on both tumor and macrophages could explain the inhibitory effect of this approach against EWS. Targeting CD99 on EWS cells downregulated expression of the "don't eat-me" CD47 molecule but increased levels of the "eat-me" phosphatidyl serine and calreticulin molecules on the outer leaflet of the tumor cell membrane, triggering phagocytosis and digestion of EWS cells by macrophages. In addition, CD99 ligation induced reprogramming of undifferentiated M0 macrophages and M2-like macrophages toward the inflammatory M1-like phenotype. These events resulted in the inhibition of EWS tumor growth. Thus, this study reveals what we believe to be a previously unrecognized function of CD99, which engenders a virtuous circle that delivers intrinsic cell death signals to EWS cells, favors tumor cell phagocytosis by macrophages, and promotes the expression of various molecules and cytokines, which are pro-inflammatory and usually associated with tumor regression. This raises the possibility that CD99 may be involved in boosting the antitumor activity of macrophages.

Kinetic parameters for H abstraction from the serine amino acid molecule

The Serine compound signifies an important model entity of polar amino acids species in various categories of biomass. The presence of adjacent amino and hydroxyl groups is expected to afford this molecule distinct fragmentation pathways. Comprehending the decomposition chemistry of serine (and other amino acids) is of a crucial important in the pursuit to minimize emission of notorious nitrogen-bearing species during thermal treatment of biomass. This contribution provides thermo-kinetic parameters for H abstraction from the five distinct sites in the serine molecule; namely amine’s, secondary’s, hydroxyl’s, and α CH hydrogen atoms by the abundant radical species in the pyrolytic/oxidative environments (H, CH3, NH2, OH, and HO2). For all considered radicals, it is illustrated that reactions of these five radicals predominantly ensue through abstraction of the α CH’s hydrogen atoms. Nonetheless, computed reaction rate constants also disclose that abstraction from the secondary’s H site becomes important as the temperature increases. Outcomes provided herein could be deployed in formulating robust kinetic models that account for the nitrogen transformation chemistry in energy recovery of biomass.

Position-specific carbon isotope analysis of serine by gas chromatography/Orbitrap mass spectrometry, and an application to plant metabolism.

Position-specific 13 C/12 C ratios within amino acids remain largely unexplored in environmental samples due to methodological limitations. We hypothesized that natural-abundance isotope patterns in serine may serve as a proxy for plant metabolic fluxes including photorespiration. Here we describe an Orbitrap method optimized for the position-specific carbon isotope analysis of serine to test our hypothesis and discuss the generalizability of this method to other amino acids. Position-specific carbon isotope ratios of serine were measured using a Thermo Scientific™ Q Exactive™ GC Orbitrap™. Amino acids were hydrolyzed from Arabidopsis biomass, purified from potential matrix interferences, and derivatized alongside standards. Derivatized serine (N,O-bis(trifluoroacetyl)methyl ester) was isolated using gas chromatography, trapped in a reservoir, and purged into the electron ionization source over tens of minutes, producing fragment ions containing different combinations of atoms from the serine-derivative molecule. The 13 C/12 C ratios of fragments with monoisotopic masses of 110.0217, 138.0166, and 165.0037 Da were monitored in the mass analyzer and used to calculate position-specific δ13 C values relative to a working standard. This methodology constrains position-specific δ13 C values for nanomole amounts of serine isolated from chemically complex mixtures. The δ13 C values of fragment ions of serine were characterized with ≤1‰ precisions, leading to propagated standard errors of 0.7-5‰ for each carbon position. Position-specific δ13 C values differed by up to ca 28 ± 5‰ between serine molecules hydrolyzed from plants grown under contrasting pCO2 , selected to promote different fluxes through photosynthesis and photorespiration. The method was validated using pure serine standards characterized offline. This study presents the first Orbitrap-based measurements of natural-abundance, position-specific carbon isotope variation in an amino acid isolated from a biological matrix. We present a method for the precise characterization of isotope ratios in serine and propose applications probing metabolism in plants. We discuss the potential for extending these approaches to other amino acids, paving the way for novel applications.

Stability and electronic properties of V-doped ruthenium nanoclusters and their adsorptive properties towards hydrogen sulphide and serine molecules

The stability and electronic properties of the RunV (n = 2–10) nanoclusters and their interaction with hydrogen sulphide and serine molecules were conducted using DFT calculations at the PBE/LanL2DZ/6-311G(d,p) level of theory. The results indicate that the Ru3V, Ru5V and Ru7V clusters were found to be more stable than their neighbouring clusters, and the V atom in the binary clusters has been viewed as the most favourable adsorption site for a nucleophilic attack. The interaction of H2S with the clusters easily leads to its dissociation into *SH and *H moieties, indicating that the dissociative adsorption was found to be more favourable than the molecular adsorption. This finding suggest that these clusters could be employed as nanocatalysts for the H2S decomposition reaction. In contrast, the serine adsorption over the surface of the RunV clusters was carried out without dissociation with adsorption energies which vary from - 29.3 to - 58.7 kcal mol−1, suggesting a chemisorption process. The adsorption of the serine molecule on the RunV (n = 3, 7 and 10) clusters causes a significant change in their energy gaps, indicating a high electronic sensitivity of these clusters towards the serine molecule.

13C Isotope Labelling to Follow the Flux of Photorespiratory Intermediates.

Measuring the carbon flux through metabolic pathways in intact illuminated leaves remains challenging because of, e.g., isotopic dilution by endogenous metabolites, the impossibility to reach isotopic steady state, and the occurrence of multiple pools. In the case of photorespiratory intermediates, our knowledge of the partitioning between photorespiratory recycling, storage, and utilization by other pathways is thus rather limited. There has been some controversy as to whether photorespiratory glycine and serine may not be recycled, thus changing the apparent stoichiometric coefficient between photorespiratory O2 fixation and CO2 release. We describe here an isotopic method to trace the fates of glycine, serine and glycerate, taking advantage of positional 13C content with NMR and isotopic analyses by LC–MS. This technique is well-adapted to show that the proportion of glycerate, serine and glycine molecules escaping photorespiratory recycling is very small.

Effects of Electrospray Droplet Size on Analyte Aggregation: Evidence for Serine Octamer in Solution.

Spraying solutions of serine under a wide variety of conditions results in unusually abundant gaseous octamer clusters that exhibit significant homochiral specificity, but the extent to which these clusters exist in solution or are formed by clustering during droplet evaporation has been debated. Electrospray ionization emitters with tip sizes between 210 nm and 9.2 μm were used to constrain the number of serine molecules that droplets initially contain. Protonated octamer was observed for all tip sizes with 10 mM serine solution, but the abundance decreases from 10% of the serine population at the largest tip size to ∼5.6% for the two smallest tip sizes. At 100 μM, the population abundance of the protonated serine octamer decreases from 1% to 0.6% from the largest to the smallest tip size, respectively. At 100 μM, fewer than 10% of the initial droplets should contain even a single analyte molecule with 210 nm emitter tips. These results indicate that the majority of protonated octamer observed in mass spectra under previous conditions is formed by clustering inside the electrospray droplet, but ≤5.6% and ∼0.6% of serine exists as an octamer complex in 10 mM and 100 μM solutions, respectively. These results show that aggregation occurs in large droplets, but this aggregation can be eliminated using emitters with sufficiently small tips. Use of these emitters with small tips is advantageous for clearly distinguishing between species that exist in solution and species formed by clustering inside droplets as solvent evaporation occurs.

Tetraphenyl porphyrin films as selective detectors for amino acid molecules

The interaction of different amino acids and vacuum evaporated tetraphenyl porphyrin films was investigated by using kinetic isotherms, UV-vis spectroscopy, quartz crystal microbalance and density functional theory techniques. The adsorption process was analyzed by using pseudo-first-order and pseudo-second-order models. From these results, the adsorption order changed depending on the chemical characteristics of the porphyrin film, although most of the interactions were classified as pseudo-second-order at the films interface. From absorbance measurements, red shifts on the Soret peak positions were observed for all amino acids interacting with the metal free and the ZnTPP systems, while the position of the Soret peak barely change for the CuTPP surface, except for a slight bathocromic shift for arginine. On the other hand, the broadening of the Soret peak was more important for the ZnTPP and H2TPP surfaces, but the interaction with the CuTPP interfaces decreased the width of the peaks in all cases. In addition, a quartz crystal microbalance analysis was employed to investigate the film sensing performance during amino acid exposure. From these results, positively charged amino acids were more easily adsorbed on the films in contrast with the polar (serine) molecule. DFT calculations exhibited important deformations for H2TPP, the out-of-plane displacement of the Zn atom for ZnTPP, and hydrogen bond interactions with the CuTPP molecule. DFT also showed high binding energies for the positively charged amino acids but low binding energies for serine in agreement with experimental data. From these results, porphyrin films could be used as selective detectors for various L-amino acid molecules.

Theoretical insight into plasma deposition of laccase bio-coating formation

Development of new techniques for deposition of biologically active coatings in the form of bio-recognition layers in biosensor construction is a current technological challenge. Biosensors are widely applied in environmental protection in determination of hazardous materials, e.g., catechol, hydrochinon or resorcinol. Application of a soft plasma polymerization (SPP) technique by low-energy-density corona discharge has allowed significant simplification of the deposition process of bio-recognition layers. However, the mechanism of the SPP process is by no means fully understood. This paper presents insights into the mechanism of binding laccase enzyme onto graphene oxide (GO) and multi-walled carbon nanotubes (MWCNT) through analysis carried out by density functional theory (DFT) methods and Fourier transform infrared spectroscopy (FTIR). The objective was to examine the mechanism on the basis of binding energies and electrostatic interactions between laccase and carbon nanomaterials as well as enzyme structure after cold plasma deposition. The lowest binding energies have been calculated for the O–N bond between the arginine amino acid of laccase and the hydroxyl group of GO and the C–O bond between the serine molecule of laccase and the carboxyl groups of GO and MWCNT. FTIR and DFT studies showed that the chemical structures of the laccase enzyme and carbon nanomaterials after corona jet plasma treatment are not substantially changed. Preliminary recognition of the mechanism of biosensing layer deposition by the SPP technique opens the way to application of this innovative technique to the construction of other biosensors such as for determination of pollutants in water samples.

Formation of a kaolinite-serine intercalation compound via exchange of the pre-intercalated transition molecules in kaolinite with serine

A kaolinite-serine intercalation compound was synthesized via the guest displacement method. Serine molecules were intercalated into kaolinite to form kaolinite-serine through exchange between serine and the guest molecules ethylene glycol or water, which was inserted into the interlayer space of kaolinite beforehand. The thickness of kaolinite-serine particles decreased to 14nm from 30nm of raw kaolinite after intercalation. The interlayer distance of kaolinite reached approximately 1.13nm after the intercalation of serine molecules. The serine molecules inserted in the interlayer space of kaolinite molecules were arranged in a flattened monolayer configuration and partially compressed into the tetragonal holes in the silicate layer. The activation energy Ea for releasing the pre-intercalated molecule before ultimate exchanging with serine determines the intercalation degree of serine into kaolinite. Higher Ea makes the expansion of kaolinite with pre-intercalated molecules more stable, which will facilitate the final intercalation of serine. The activation energy is 6.95kJ/mol for ethylene glycol and 21.2kJ/mol for water, respectively, resulting in serine intercalation degree of 45%, and 85% correspondingly. The kaolinite-serine intercalation compound is expected to be applied in the pharmaceutical and cosmetics fields.

Designing L-serine targeted molecularly imprinted polymer via theoretical investigation

Molecular imprinting is one of few general, nonbiological methods for creating molecular receptors, but the progress in molecular imprinting calls for the predictive tools capable of understanding molecular level complexities of these processes. Thus, computational chemistry which predicts the suitability of functional monomer in designing the sensor for a particular analyte was attempted to design an amino acid (L-serine) sensor based on the molecular imprinting approach using density functional theory (DFT). Here, the computations were carried out to check the feasibility of best suited monomers for imprinting an amino acid (L-serine) in water and allied solvents. DFT method was utilized at B3LYP/6-31[Formula: see text]G(d,p) level to optimize template, monomers and template-monomer complexes and basis set superposition error (BSSE) was corrected by means of the counterpoise (CP) method for complexes in gas phase. All monomers can be utilized for imprinting. 2-vinyl pyridine and acrylamide were found to be good for imprinting serine in water but toluene was found to be good porogen for imprinting serine with functional monomer acrylamide. This study will aid in designing a water-compatible MIP sensor for serine molecules, which could be a biomarker for certain neurological disorders.

Photofragmentation of Serine Following C 1s Core Ionization-Comparison with Cysteine.

Photofragmentation pathways of doubly ionized serine molecules are investigated and compared with those of cysteine. The main motivation for the study is to investigate if an atomic substitution within the same group of elements, namely, replacing sulfur (in cysteine) with oxygen (in serine), causes a major change in the C 1s core ionization induced dissociation pattern in the molecules of an otherwise identical structure. The results show that in serine there is a single completely dominant fragmentation channel producing the (CNH2–4+, COH1–3+) pairs, whereas in cysteine there are also many other fragmentation channels. The employed experimental method was the photoelectron–photoion–photoion coincidence (PEPIPICO) technique combined with synchrotron radiation tuned to ionize desired core levels. Molecular dynamics calculations were also carried out in order to extract information on the fragmentation and the neutral final fragments.

In vivo stoichiometry of photorespiratory metabolism.

Photorespiration is a major light-dependent metabolic pathway that consumes oxygen and produces carbon dioxide. In the metabolic step responsible for carbon dioxide production, two molecules of glycine (equivalent to two molecules of O2) are converted into one molecule of serine and one molecule of CO2. Here, we use quantitative isotopic techniques to determine the stoichiometry of this reaction in sunflower leaves, and thereby the O2/CO2 stoichiometry of photorespiration. We find that the effective O2/CO2 stoichiometric coefficient at the leaf level is very close to 2 under normal photorespiratory conditions, in line with expectations, but increases slightly at high rates of photorespiration. The net metabolic impact of this imbalance is likely to be modest.

Structure of L-serine dehydratase from Legionella pneumophila: novel use of the C-terminal cysteine as an intrinsic competitive inhibitor.

Here we report the first complete structure of a bacterial Fe–S l-serine dehydratase determined to 2.25 Å resolution. The structure is of the type 2 l-serine dehydratase from Legionella pneumophila that consists of a single polypeptide chain containing a catalytic α domain and a β domain that is structurally homologous to the “allosteric substrate binding” or ASB domain of d-3-phosphoglycerate dehydrogenase from Mycobacterium tuberculosis. The enzyme exists as a dimer of identical subunits, with each subunit exhibiting a bilobal architecture. The [4Fe-4S]2+ cluster is bound by residues from the C-terminal α domain and is situated between this domain and the N-terminal β domain. Remarkably, the model reveals that the C-terminal cysteine residue (Cys 458), which is conserved among the type 2 l-serine dehydratases, functions as a fourth ligand to the iron–sulfur cluster producing a “tail in mouth” configuration. The interaction of the sulfhydryl group of Cys 458 with the fourth iron of the cluster appears to mimic the position that the substrate would adopt prior to catalysis. A number of highly conserved or invariant residues found in the β domain are clustered around the iron–sulfur center. Ser 16, Ser 17, Ser 18, and Thr 290 form hydrogen bonds with the carboxylate group of Cys 458 and the carbonyl oxygen of Glu 457, whereas His 19 and His 61 are poised to potentially act as the catalytic base required for proton extraction. Mutation of His 61 produces an inactive enzyme, whereas the H19A protein variant retains substantial activity, suggesting that His 61 serves as the catalytic base. His 124 and Asn 126, found in an HXN sequence, point toward the Fe–S cluster. Mutational studies are consistent with these residues either binding a serine molecule that serves as an activator or functioning as a potential trap for Cys 458 as it moves out of the active site prior to catalysis.

Regulation of Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase by phosphate-modulated quaternary structure dynamics and a potential role for polyphosphate in enzyme regulation.

D-3-phosphoglycerate dehydrogenase (PGDH) catalyzes the first reaction in the "phosphorylated" pathway of l-serine biosynthesis. In Mycobacterium tuberculosis, it is a type 1 enzyme (mtPGDH) in that it contains both an ACT domain and an ASB domain in addition to a catalytic domain. The published crystal structures (Protein Data Bank entries 1YGY and 3DC2) show a tartrate molecule interacting with cationic residues at the ASB-ACT domain interfaces and a serine molecule bound at the ACT domain interface. These sites have previously been shown to be involved in the mechanism of serine and substrate inhibition of catalytic activity. This investigation has revealed a mechanism of allosteric quaternary structure dynamics in mtPGDH that is modulated by physiologically relevant molecules, phosphate and polyphosphate. In the absence of phosphate and polyphosphate, the enzyme exists in equilibrium between an inactive dimer and an active tetramer that is insensitive to inhibition of catalytic activity by L-serine. Phosphate induces a conversion to an active tetramer and octamer that are sensitive to inhibition of catalytic activity by L-serine. Small polyphosphates (pyrophosphate and triphosphate) induce a conversion to an active dimer that is insensitive to L-serine inhibition. The difference in the tendency of each respective dimer to form a tetramer as well as slightly altered elution positions on size exclusion chromatography indicates that there is likely a conformational difference between the serine sensitive and insensitive states. This appears to constitute a unique mechanism in type 1 PGDHs that may be unique in pathogenic Mycobacterium species and may provide the organisms with a unique metabolic advantage.

Cytokines regulate HIV-1 replication and lymphocyte apoptosis in vitro

Aim. To study the ability of cytokines - interleukin-2, interleukin-7 and tumor necrosis factor alpha to induce human immunodeficiency virus type 1 (HIV-1) replication and lymphocyte apoptosis in vitro. Methods. Peripheral blood mononuclears were separated by centrifugation on a ficoll paque solution specific density gradient. Lymphocytes were cultivated in RPMI 1640 medium with addition of L-glutamine, embryonal bovine serum, antibiotics and cytokines (interleukines-2, -4, -7, tumor necrosis factor alpha). To infect the lymphocytes, a laboratory strain of HIV-1 NL4-3 (NIH ResReag. Prog., USA) was used. HIV-1 replication was assessed by р24gag viral protein level in culture supernatants (ELISA) and its cytozolic level in lymphocytes (flow cytometry). Lymphocyte apoptosis was assessed by flow cytometry using the following parameters: (1) decrease of transmembrane mitochondrial potential; (2) increase in phosphatidyl serine molecules expression. Lymphocyte activation was assessed by CD25 and HLA-DR molecules expression (flow cytometry). Results. Cytokines induce the HIV-1 replication in lymphocytes in vitro. HIV-1 replication was noted only if inactivated lymphocytes were present in the culture. At the same time, lymphocytes not expressing the classical activation markers (CD25 and HLA-DR) were present among the lymphocytes producing HIV-1 indicating the possible alternative mechanism of HIV-1 replication, not dependent on cell activation. This fact might also be an evidence of viral replication processes in the pool of latently-infected lymphocytes, not expressing the classic activation markers. The abovementioned cytokines promote apoptotic death of uninfected lymphocytes in vitro, backing up the infected cells viability and thus promoting HIV-1 replication. Conclusion. Cytokines (interleukines-2, -4, -7, tumor necrosis factor alpha) which are known as factors supporting the immune system homeostasis and immune response formation, might also play a negative role in HIV-1 pathogenesis - induce HIV-1 replication in lymphocytes and, probably, lead to reactivation of the pool of latently-infected lymphocytes, deepening the lymphopenia and leading to disease progression.

Probing O-dealkylation and deamination aging processes in tabun-conjugated AChE: a computational study

The mechanisms of the aging process of tabun-conjugated acetylcholinesterase were explored using density functional theory calculations. The free energy surfaces were calculated for O-dealkylation (C–O bond breaking) and deamination (P–N bond breaking) pathways for the aging process of tabun-conjugated acetylcholinesterase as suggested by mass and crystallographic studies. Initially, the calculations were performed using tabun-conjugated serine (SUN) molecule. O-dealkylation mechanism proceeds via one-step SN2 type process, whereas the deamination process proceeds via two steps addition–elimination reaction at the phosphorus center of SUN molecule. The recent proposal of another deamination mechanism using human butyrylcholinesterase (hBChE) conjugated with N-mono methyl analogue of tabun (TA4) has also been explored (Nachon et al. in Chem Biol Interact 187:44–48, 2010). The rate-determining activation barrier calculated for this deamination mechanism (26.3 kcal/mol) was comparable with O-dealkylation process (26.9 kcal/mol) with B3LYP/6-31+G* level of theory. To examine the influence of catalytic residue His447, additional calculations were performed with imidazole group of His447 residue. The incorporation of imidazole group of catalytic residue His447 showed marked decrease in the free energies of activation for all the studied aging processes of tabun-inhibited serine. The aging mechanisms have been explored with TA4-inhibited serine, and calculated results showed that the deamination with the rearrangement process is markedly preferred in this case, which supports the Nachon et al. proposal based on the crystallographic studies.

Density functional theory (DFT) calculations of the proton nuclear magnetic resonance (NMR) spin-Hamiltonian parameters for serine

1H nuclear magnetic resonance spin-Hamiltonian parameters: chemical shifts δ and indirect spin–spin coupling constants J, have been calculated for serine, a brain metabolite. Serine molecules in the gas-phase as well as in solution in water have been investigated using density functional theory. Solvent and conformer effects as well as zero-point vibrational corrections have been taken into account. For the non-vibrating molecule, the best agreement is obtained when solvent and conformer effects are included. Zero-point vibrational corrections improve the agreement with experimental values, leading to a root mean square deviation of 0.05 ppm for chemical shifts and 0.7 Hz for spin–spin coupling constants.

Formation of the Magic L‐Serine Octamer in Helium Nanodroplets

It′s a kind of magic: Electron ionization of helium nanodroplets doped with L-serine clusters forms protonated serine cluster ions. For small droplets vaporization of serine molecules leads to a magic octamer which is suppressed in the case of large He droplets (see picture).

What Are the Consequences of Phosphorylation and Hyperphosphorylation of Ryanodine Receptors in Normal and Failing Heart?

See related article, pages e65–e72 Marks and colleagues published some influential results in 2000, suggesting that protein kinase A phosphorylation regulates ryanodine receptor (RyR2) open probability ( P oRyR). The authors attributed this to the dissociation of the RyR-associated regulatory protein FKBP12.6.1 They went on to propose that, in failing hearts, RyR2 is hyperphosphorylated, which leads to defective channel function by increasing sensitivity to Ca-induced activation of the molecule. Moreover, these effects were attributable to phosphorylation of a single amino acid, serine 2809 (S2809). There are 4 of these serine molecules at location 2808 in the human RyR2 molecule, 1 on each subunit of the tetramer. Much subsequent work has referred to the 2809 residue, which is found in rabbits. Marks and colleagues further suggested that phosphorylation of S2809 was also responsible for the normal effects of adrenergic stimulation on excitation–contraction coupling (ECC) and that hyperphosphorylation was responsible for abnormal ECC during failure. The RyR is a tetramer that forms the largest membrane ion channel. In muscle, it is found in the sarcoplasmic reticulum (SR), where it functions as the Ca release channel. The heart isoform is designated RyR2. The pore sequences are largely found in membrane spanning domains.2 There is a large cytosolic domain. Although hyperphosphorylation refers, by definition, to the occupation of all the putative phosphorylation sites in a molecule in the context of the work by Marks and colleagues,1 hyperphosphorylation refers to 3 or perhaps 4 of the serine residues. In RyRs, there are a large number of consensus phosphorylation sites.3 RyRs are associated with a number of proteins, and these include anchoring protein phosphatases and kinases, as well as the regulatory protein FKBP12.6. From the standpoint of this editorial, this last protein is perhaps the most interesting, and it is considered …

High-pressure polymorphism in L-serine monohydrate: identification of driving forces in high pressure phase transitions and possible implications for pressure-induced protein denaturation

At ambient pressure the crystal structure of L-serine monohydrate (L-serine monohydrate-I) contains H-bonded layers of zwitterionic serine molecules linked by H-bonds to water molecules. The waters act as donors to oxygen atoms on carboxylate and alcohol groups in separate layers. This phase remains stable from ambient pressure to 4.5 GPa; the most prominent structural change in this range is a reduction in the interlayer distance. On increasing the pressure to 5.2 GPa the structure transforms to a high-pressure polymorph, termed L-serine monohydrate-II. The structures of both polymorphs have been determined using a combination of X-ray single-crystal and neutron powder diffraction. During the transition the serine interlayer distances reduce further and the water molecules rotate so that both donor interactions are made to the same serine layer. The serine ammonium group adopts an eclipsed conformation, reconfiguring the H-bonding within the serine layers. The disruption of H-bonding as water is pushed into the serine layers suggests that a similar process may occur as a first step in the pressure-denaturation of proteins. Though the water molecules become coordinatively saturated with respect to H-bonding, and interlayer serine-serine Coulombic interactions are strengthened, PIXEL calculations show that overall the intermolecular interactions are weaker in phase-II than phase-I. The lattice enthalpy becomes more negative through the transition as a result of the smaller PV term applying to the more efficiently packed phase-II structure.