Using Multiconformation Continuum Electrostatics to Compare Chloride Binding Motifs in α-Amylase, Human Serum Albumin, and Omp32

Song, Yifan; Gunner, M. R.

doi:10.1016/j.jmb.2009.01.038

Cited by 45 publications

(58 citation statements)

References 117 publications

(156 reference statements)

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“…Cl -binding in the HR ground state is dependent on both the pH and Cl -concentration, as found in other ion-binding systems (9,10). At low Clconcentrations, no Cl -is bound and the HR absorption spectrum is blue-shifted, indicating that the trans retinal SB is deprotonated (45).…”

Section: Resultsmentioning

confidence: 85%

“…S3). Cl -occupancy, residue protonation, and conformation are subjected to Monte Carlo sampling at the same time (10). At pH 7 and below chloride concentrations of ∼1 M, two chloride binding sites are found within the protein (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In MCCE, the Cl -concentration is included in the energy terms for Monte Carlo sampling (Eq. S1) (10). Using the energy for the Cl -solution chemical potential, optimized for a similar buried binding site in α-amylase, the SB pK a is calculated to be 8.5 at 0.050 M Cl - (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Methods that use CE analysis and Monte Carlo sampling are also particularly well suited to investigate the coupling of proton and ion binding, as each comes to equilibrium at a given pH and ionic strength in the same calculation. Such CE studies have identified the Cl -binding site in Na + /Cl --dependent transporters (39) and modeled the Cl -affinity as a function of pH in membrane-bound and soluble proteins (10) and in different redox states of photosystem II (40). In the work presented here, MCCE-calculated ground-state residue ionization states and chloride binding in HR are compared with previous BR calculations (23,38).…”

Section: Significancementioning

confidence: 99%

“…For example, mutation of a phosphorylation site to an anionic amino acid has been found to yield constitutive activation (7) that can trigger certain cancers (8). Amylases provide another example, where one class is dependent on the pH and Cl -concentration, with an active site Arg or Lys binding the chloride (9,10). In contrast, amylases remove the basic amino acid and have pH-and Cl --independent activity.…”

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confidence: 99%

See 4 more Smart Citations

Halorhodopsin pumps Cl^–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

Song¹,

Gunner

2014

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

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Key mutations differentiate the functions of homologous proteins. One example compares the inward ion pump halorhodopsin (HR) and the outward proton pump bacteriorhodopsin (BR). Of the nine essential buried ionizable residues in BR, six are conserved in HR. However, HR changes three BR acids, D85 in a central cluster of ionizable residues, D96, nearer the intracellular, and E204, nearer the extracellular side of the membrane to the small, neutral amino acids T111, V122, and T230, respectively. In BR, acidic amino acids are stationary anions whose proton affinity is modulated by conformational changes, establishing a sequence of directed binding and release of protons. Multiconformation continuum electrostatics calculations of chloride affinity and residue protonation show that, in reaction intermediates where an acid is ionized in BR, a Cl -is bound to HR in a position near the deleted acid. In the HR ground state, Cl -binds tightly to the central cluster T111 site and weakly to the extracellular T230 site, recovering the charges on ionized BR-D85 and neutral E204 in BR. Imposing key conformational changes from the BR M intermediate into the HR structure results in the loss of Cl -from the central T111 site and the tight binding of Cl -to the extracellular T230 site, mirroring the changes that protonate BR-D85 and ionize E204 in BR. The use of a mobile chloride in place of D85 and E204 makes HR more susceptible to the environmental pH and salt concentrations than BR. These studies shed light on how ion transfer mechanisms are controlled through the interplay of protein and ion electrostatics.

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Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Halorhodopsin pumps Cl^–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

Song¹,

Gunner

2014

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

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Is there an embryopathy associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors and angiotensin receptor antagonists? A critical review of the evidence

Polifka

2012

Birth Defects Research

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Drugs that interfere with the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are widely used to manage hypertension and heart failure. Adequate functioning of the RAS is essential for normal fetal kidney development. The potential for ACEIs and ARBs to impair fetal and neonatal renal function if taken after the first trimester of pregnancy has been well documented. Although these drugs were not found to be teratogenic in animals, until recently little was known about the teratogenic effects of ACEIs and ARBs in humans when exposure was limited to the first trimester of pregnancy. New evidence from epidemiologic studies indicates that there may be an elevated teratogenic risk when these drugs are taken during the first trimester of pregnancy. However, this elevated risk does not appear to be specific to ACEIs and ARBs, but is instead related to maternal factors and diseases that typically coexist with hypertension in pregnancy, such as diabetes, advanced maternal age, and obesity. Women who become pregnant while being treated with an ACEI or ARB should be advised to avoid exposure to these drugs during the second and third trimesters of pregnancy by switching to a different class of antihypertensive drugs between weeks 8 and 10 after conception.

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Mechanism of initial rapid rate retardation in cellobiohydrolase catalyzed cellulose hydrolysis

Jalak

Väljamaë

2010

Biotech & Bioengineering

132

157

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Despite intensive research, the mechanism of the rapid retardation in the rates of cellobiohydrolase (CBH) catalyzed cellulose hydrolysis is still not clear. Interpretation of the hydrolysis data has been complicated by the inability to measure the catalytic constants for CBH-s acting on cellulose. We developed a method for measuring the observed catalytic constant (k(obs)) for CBH catalyzed cellulose hydrolysis. It relies on in situ measurement of the concentration of CBH with the active site occupied by the cellulose chain. For that we followed the specific inhibition of the hydrolysis of para-nitrophenyl-beta-D-lactoside by cellulose. The method was applied to CBH-s TrCel7A from Trichoderma reesei and PcCel7D from Phanerochaete chrysosporium and their isolated catalytic domains. Bacterial microcrystalline cellulose, Avicel, amorphous cellulose, and lignocellulose were used as substrates. A rapid decrease of k(obs) in time was observed on all substrates. The k(obs) values for PcCel7D were about 1.5 times higher than those for TrCel7A. In case of both TrCel7A and PcCel7D, the k(obs) values for catalytic domains were similar to those for intact enzymes. A model where CBH action is limited by the average length of obstacle-free way on cellulose chain is proposed. Once formed, productive CBH-cellulose complex proceeds with a constant rate determined by the true catalytic constant. After encountering an obstacle CBH will "get stuck" and the rate of further cellulose hydrolysis will be governed by the dissociation rate constant (k(off)), which is low for processive CBH-s.

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Using Multiconformation Continuum Electrostatics to Compare Chloride Binding Motifs in α-Amylase, Human Serum Albumin, and Omp32

Cited by 45 publications

References 117 publications

Halorhodopsin pumps Cl^–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

Halorhodopsin pumps Cl^–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

Is there an embryopathy associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors and angiotensin receptor antagonists? A critical review of the evidence

Mechanism of initial rapid rate retardation in cellobiohydrolase catalyzed cellulose hydrolysis

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Using Multiconformation Continuum Electrostatics to Compare Chloride Binding Motifs in α-Amylase, Human Serum Albumin, and Omp32

Cited by 45 publications

References 117 publications

Halorhodopsin pumps Cl–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

Halorhodopsin pumps Cl–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

Is there an embryopathy associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors and angiotensin receptor antagonists? A critical review of the evidence

Mechanism of initial rapid rate retardation in cellobiohydrolase catalyzed cellulose hydrolysis

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Product

Resources

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Halorhodopsin pumps Cl^–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions

Halorhodopsin pumps Cl^–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions