Hydration Forces Underlie the Exclusion of Salts and of Neutral Polar Solutes from Hydroxypropylcellulose

Chik, John K.; Mizrahi, S.; Chi, Sulene; Parsegian, and V. Adrian; Rau, Donald C.

doi:10.1021/jp046999k

Cited by 37 publications

(60 citation statements)

References 36 publications

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“…Salt deficits in macromolecular aggregates have been reported for other systems as well, from single-chain charged surfactants (39) to neutral polymers (40). Here, the distribution of salt in the interlamellar space is determined by the competition between salt and lipid headgroups for interfacial water.…”

Section: Salt Screening (Low Vs High Frequencies)mentioning

confidence: 87%

Salt screening and specific ion adsorption determine neutral-lipid membrane interactions

Petrache

Zemb

Belloni

et al. 2006

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

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The simplest, single-component biological membrane challenges accepted models of macromolecular interactions: lipid lamellar phases swell when immersed in monovalent salt solutions. Moreover, typical of a Hofmeister series, Br salts swell multilayers more than Cl salts, offering an excellent opportunity to investigate long-standing questions of ionic specificity. In accord with earlier measurements of liposome mobilities in electric fields, we find an added electrostatic repulsion of membranes due to anion binding, with a much stronger Br binding compared with Cl. However, contrary to the expectation that electrostatic repulsion should vanish in high salinity, swelling of lipid multilayers is monotonic with increasing salt concentration for both Br and Cl salts. The apparent contradiction is resolved by recognizing that although the electrostatic repulsion is progressively screened by increasing salt concentration, so is the van der Waals (vdW) attraction. Negligible in low salt, weakening of vdW forces becomes significant by the time electrostatic forces vanish. The result is a smooth monotonic swelling curve with no apparent distinction between low and high salt concentration regimes. Furthermore, when compared with theoretical predictions, measured vdW forces decay much too slowly with added salt. However, by accounting for the recently measured salt deficit near lipid bilayers, the expected scaling with Debye screening length is recovered. The combination of ion-specific binding and nonspecific ionic screening of lowfrequency fluctuations explains salt effects on lipid membrane interactions and, by extension, explains specific (Hofmeister) effects at macromolecular interfaces between low and high dielectric.electrostatics ͉ halides ͉ ion binding ͉ van der Waals ͉ hydration

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Section: Salt Screening (Low Vs High Frequencies)mentioning

confidence: 87%

Salt screening and specific ion adsorption determine neutral-lipid membrane interactions

Petrache

Zemb

Belloni

et al. 2006

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

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257

306

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“…Preferential hydration (24,41) recognizes that the interaction of water with groups on nucleic acid and protein surfaces may be more energetically favorable than interaction of solutes with macromolecules. Many experiments measuring both exclusion of solutes from protein and DNA surfaces as well as the effect of this exclusion on different macromolecular reactions show that the apparent number or change in the number of hydrating waters is constant over a wide range of solute concentrations for each osmolyte, but that this number is sensitively dependent on the particular solute probing surface hydration (2,(25)(26)(27)(28)(29)(30)41). For the osmolytes we usually use (sucrose, glycine betaine, triethylene glycol, etc.)…”

Section: Discussionmentioning

confidence: 99%

“…the number of waters associated with surface hydration depends on the osmolyte probing the surface. There are now many examples in literature establishing this sensitivity (2,(23)(24)(25)(26)(27)(28)(29)(30). Some researchers emphasize the excluded solute rather than the included water, but the thermodynamics is the same and converting between the numbers of excluded solute and included water is straightforward (3).…”

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confidence: 99%

Differences in Hydration Coupled to Specific and Nonspecific Competitive Binding and to Specific DNA Binding of the Restriction Endonuclease BamHI

Sidorova

Muradymov

Rau

2006

Journal of Biological Chemistry

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Using the osmotic stress technique together with a self-cleavage assay we measure directly differences in sequestered water between specific and nonspecific DNA-BamHI complexes as well as the numbers of water molecules released coupled to specific complex formation. The difference between specific and nonspecific binding free energy of the BamHI scales linearly with solute osmolal concentration for seven neutral solutes used to set water activity. The observed osmotic dependence indicates that the nonspecific DNA-BamHI complex sequesters some 120 -150 more water molecules than the specific complex. The weak sensitivity of the difference in number of waters to the solute identity suggests that these waters are sterically inaccessible to solutes. This result is in close agreement with differences in the structures determined by x-ray crystallography. We demonstrate additionally that when the same solutes that were used in competition experiments are used to probe changes accompanying the binding of free BamHI to its specific DNA sequence, the measured number of water molecules released in the binding process is strikingly solute-dependent (with up to 10-fold difference between solutes). This result is expected for reactions resulting in a large change in a surface exposed area.Whereas it is generally accepted that hydration water plays an important role in DNA-protein sequence-specific recognition (1) there are only few techniques available to probe its contribution reliably. We use an approach termed the osmotic stress technique (2, 3) that measures changes in hydration coupled with changes in the functional state by measuring the effect of water activity on reaction equilibria and kinetics. The osmotic stress technique has been used previously to measure the changes in hydration accompanying the DNA binding of several regulatory proteins: Escherichia coli gal (4), lac (5), tyr (6), and Cro (7) repressors, E. coli CAP protein (8), Hin recombinase (9), Ultrathorax and Deformed homeodomains (10), the restriction endonucleases , BamHI (15,16), and EcoRV (17), HhaI methyltransferase (18), Sso7d protein (19), the TATA-binding protein (20,21), and the E2C protein from papillomavirus (22).The dependence of an equilibrium constant on the bulk solution osmotic pressure that is varied by adding neutral solutes that do not bind directly to the DNA or protein gives a difference in the number of associated waters between the initial reactants and the final products. More precisely, water is considered associated with the DNA, protein, and complex if it excludes osmolyte, otherwise there is no osmotic imbalance. Obviously, water that is sterically sequestered in cavities, channels, or pockets fulfills this requirement. All solutes that are excluded from these cavities act identically on the equilibrium. Water molecules hydrating exposed macromolecular surfaces are more problematic. For the most part, solutes are excluded from these waters due to "preferential hydration," macromolecules prefer their interactions with water over...

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“…However, the slopes for the glycine betaine, Me 2 SO, and sucrose data are higher, ranging from 40 to 60. Variable slopes are common in osmolality studies, but their origin is not clear (37,38,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). This issue will be broached under the "Discussion.…”

Section: Role Of Water In K Cat /K M(dhf)mentioning

confidence: 99%

A Balancing Act between Net Uptake of Water during Dihydrofolate Binding and Net Release of Water upon NADPH Binding in R67 Dihydrofolate Reductase

Chopra

Dooling

Horner

et al. 2008

Journal of Biological Chemistry

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R67 dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate using NADPH as a cofactor. This enzyme is a homotetramer possessing 222 symmetry, and a single active site pore traverses the length of the protein. A promiscuous binding surface can accommodate either DHF or NADPH, thus two nonproductive complexes can form (2NADPH or 2DHF) as well as a productive complex (NADPH⅐DHF). The role of water in binding was monitored using a number of different osmolytes. From isothermal titration calorimetry (ITC) studies, binding of NADPH is accompanied by the net release of 38 water molecules. In contrast, from both steady state kinetics and ITC studies, binding of DHF is accompanied by the net uptake of water. Although different osmolytes have similar effects on NADPH binding, variable results are observed when DHF binding is probed. Sensitivity to water activity can also be probed by an in vivo selection using the antibacterial drug, trimethoprim, where the water content of the media is decreased by increasing concentrations of sorbitol. The ability of wild type and mutant clones of R67 DHFR to allow host Escherichia coli to grow in the presence of trimethoprim plus added sorbitol parallels the catalytic efficiency of the DHFR clones, indicating water content strongly correlates with the in vivo function of R67 DHFR.R67 dihydrofolate reductase, a type II DHFR, 2 catalyzes the NADPH-dependent reduction of dihydrofolate (DHF) to tetrahydrofolate. The gene for this enzyme is carried by an R-plasmid, and its presence confers resistance to the antibiotic drug, trimethoprim (TMP). Trimethoprim is a competitive inhibitor of chromosomal DHFR with a picomolar K i (1). Although R67 DHFR is not a good catalyst, it is not inhibited by TMP very well, and thus it allows cell growth in the presence of this antibacterial drug (2, 3). R67 DHFR shares no homology in sequence or structure with chromosomal DHFR and has been proposed to be a good model of a primitive enzyme (4).R67 DHFR is a homotetramer with a single active site pore; the overall structure possesses 222 symmetry as seen in Fig. 1 (5). The symmetry of the active site results in overlapping binding sites for substrate, DHF, and cofactor, NADPH. This can be observed as R67 DHFR binds a total of two ligands as follows: either two NADPH molecules or two folate/DHF molecules or one NADPH plus one folate/DHF molecule (6). The first two complexes are dead-end (binary) complexes, whereas the third is the productive ternary complex. Because of the 222 symmetry, binding to either ligand is unlikely to be optimal.The active site pore of R67 DHFR is unusual in its hourglass shape as well as its large size (2938 Å 3 for apoR67 DHFR with hydrogens added, calculated by CASTp (4, 7)). Because of this large volume, DHF and NADPH cannot occupy all the space in the pore and must use water to mediate some contacts with the protein.How do substrate and cofactor bind to R67 DHFR? From NMR, crystallography, and docking studies, the pteridine ring of DHF/fo...

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Hydration Forces Underlie the Exclusion of Salts and of Neutral Polar Solutes from Hydroxypropylcellulose

Cited by 37 publications

References 36 publications

Salt screening and specific ion adsorption determine neutral-lipid membrane interactions

Salt screening and specific ion adsorption determine neutral-lipid membrane interactions

Differences in Hydration Coupled to Specific and Nonspecific Competitive Binding and to Specific DNA Binding of the Restriction Endonuclease BamHI

A Balancing Act between Net Uptake of Water during Dihydrofolate Binding and Net Release of Water upon NADPH Binding in R67 Dihydrofolate Reductase

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