Abstract：
:A grand canonical formalism is developed to combine discrete simulations for chemically distinct species in equilibrium. Each simulation is based on a perturbed funneled landscape. The formalism is illustrated using the alkaline-induced transitions of cytochrome c as observed by FTIR spectroscopy and with various other experimental approaches. The grand canonical simulation method accounts for the acid/base chemistry of deprotonation, the inorganic chemistry of heme ligation and misligation, and the minimally frustrated folding energy landscape, thus elucidating the physics of protein folding involved with an acid/base titration of a protein. The formalism combines simulations for each of the relevant chemical species, varying by protonation and ligation states. In contrast to models based on perfectly funneled energy landscapes that contain only contacts found in the native structure, this study introduces "chemical frustration" from deprotonation and misligation that gives rise to many intermediates at alkaline pH. While the nature of these intermediates cannot be easily inferred from available experimental data, this study provides specific structural details of these intermediates, thus extending our understanding of how cytochrome c changes with an increase in pH. The results demonstrate the importance of chemical frustration for understanding biomolecular energy landscapes.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Weinkam P,Romesberg FE,Wolynes PGdoi
10.1021/bi802293msubject
Has Abstractpub_date
2009-03-24 00:00:00pages
2394-402issue
11eissn
0006-2960issn
1520-4995pii
10.1021/bi802293mjournal_volume
48pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:Protein farnesyltransferase catalyzes the posttranslational farnesylation of several proteins involved in signal transduction, including Ras, and is a target enzyme for antitumor therapies. Efficient product formation catalyzed by protein farnesyltransferase requires an enzyme-bound zinc cation and high concentrations...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0011781
更新日期：2000-10-10 00:00:00
abstract：:The full-length cDNA encoding a novel human intracellular serine proteinase inhibitor has been sequenced and found to encode a 376 amino acid protein (M(r) approximately 42.5K) that we designate as cytoplasmic antiproteinase. Analysis of the primary structure revealed that the cytoplasmic antiproteinase has the majori...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00177a037
更新日期：1994-03-22 00:00:00
abstract：:Site-directed mutants of human carbonic anhydrase III were used to examine the role of Thr-199 and its interaction with Phe-198 in the catalyzed hydration of CO2. Threonine-199 is a hydrogen bond acceptor for the zinc-bound water, and Phe-198 forms part of the hydrophobic side of the active-site cavity of carbonic anh...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00082a004
更新日期：1993-08-10 00:00:00
abstract：:Legumain (asparaginyl endopeptidase) is the only protease with a preference for cleavage after asparagine residues. Increased legumain activity is a hallmark of inflammation, neurodegenerative diseases, and cancer, and legumain inhibitors have exhibited therapeutic effects in mouse models of these pathologies. Improve...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.9b00821
更新日期：2020-01-28 00:00:00
abstract：:The method of transient electric birefringence has been applied to study the conformation of protein-sodium dodecyl sulfate complexes. A model of a deformable prolate ellipsoid has been proposed for the protein-dodecyl sulfate complex. This model is compared to the models proposed by J. A. Reynolds and C. Tanford (197...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00685a030
更新日期：1975-07-15 00:00:00
abstract：:The coordinated activity of protein tyrosine phosphatases (PTPs) is crucial for the initiation, modulation, and termination of diverse cellular processes. The catalytic activity of this protein depends on a nucleophilic cysteine at the active site that mediates the hydrolysis of the incoming phosphotyrosine substrate....
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi201092q
更新日期：2011-11-22 00:00:00
abstract：:To determine whether ligand-receptor interactions could engender the selective uptake by deficient cells of enzyme-laden liposomes, aggregated human IgG was used to coat liposomes which had previously trapped purified hexosaminidase A (Hex A). By a new, high-yield procedure, Hex A was purified 7000-fold from human pla...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00647a034
更新日期：1976-01-27 00:00:00
abstract：:A cross-linked tripeptide has been isolated from alkaline hydrolysates of NaB3H4-reduced calf bone collagen. The peptide contains dihydroxylysinonorleucine, the most abundant cross-link in bone collagen, and it has a single N-terminal proline and a single C-terminal valine. These amino acids are in peptide linkage wit...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00691a011
更新日期：1975-10-07 00:00:00
abstract：:The sensitivity of the fluorescence energy of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) to apparent solvent polarity is considerably greater in methanol-water mixtures and lower primary alcohols than in higher primary alcohols or solvents containing no hydroxyl groups. It is suggested that the behavior of TNS in low...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00675a016
更新日期：1975-02-25 00:00:00
abstract：:VanX, one of the five proteins required for the vancomycin-resistant phenotype in clinically pathogenic Enterococci, is a zinc-containing d-Ala-d-Ala dipeptidase. To identify potential zinc ligands and begin defining the active site residues, we have mutated the 2 cysteine, 5 histidine, and 4 of the 28 aspartate and g...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi970543u
更新日期：1997-08-26 00:00:00
abstract：:The synthesis of activated sulfate (adenosine 5'-phosphosulfate, APS) and inorganic pyrophosphate from ATP and SO4 is remarkably unfavorable: K(eq) approximately 10(-8) under presumed, near-physiological conditions. Consequently, ATP sulfurylases, which catalyze APS synthesis, suffer approximately 10(8)-fold losses in...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi060421e
更新日期：2006-09-26 00:00:00
abstract：:Incubation of bovine plasma amine oxidase (BPAO) with benzylamine and various p-substituted analogues results in a time-dependent inactivation that is attributable to buildup of the H(2)O(2)-turnover product on the basis of protection afforded by coincubation with catalase. The mechanism of inactivation is distinct fr...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi002118y
更新日期：2001-01-23 00:00:00
abstract：:Aromatic amino acid aminotransferase (ArAT) from Escherichia coli was overexpressed in E. coli cells, purified, and characterized. The enzyme was similar to aspartate aminotransferase (AspAT) of E. coli in many aspects, such as gross protein structure and spectroscopic properties. The reactions of pyridoxal 5'-phospha...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00096a036
更新日期：1993-11-16 00:00:00
abstract：:Factor VIII (fVIII) is synthesized as a single chain having a domainal sequence A1-A2-B-A3-C1-C2. Analysis of the proteolyic cleavage of fVIII by thrombin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) identifies three fragments designated fVIIIA1, fVIIIA2, and fVIIIA3-C1-C2 with fragment(s) d...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00428a038
更新日期：1989-01-24 00:00:00
abstract：:The kinetics of charge recombination following photoexcitation by a laser pulse have been analyzed in the reaction center-light harvesting complex 1 (RC-LH1) purified from the photosynthetic bacterium Rhodobacter sphaeroides. In RC-LH1 core complexes isolated from photosynthetically grown cells P(+)Q(B)(-) recombines ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi048629s
更新日期：2004-11-09 00:00:00
abstract：:Barnase, the ribonuclease from Bacillus amyloliquefaciens, has been cloned and expressed in Escherichia coli [Hartley, R. W. (1988) J. Mol. Biol. 202, 913-915], thus enabling the overproduction and site-directed mutagenesis of one of the smallest enzymes (Mr equals 12,382). As barnase is also composed of just a single...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00435a033
更新日期：1989-05-02 00:00:00
abstract：:Human methionine synthase reductase (MSR), a diflavin oxidoreductase, plays a vital role in methionine and folate metabolism by sustaining methionine synthase (MS) activity. MSR catalyzes the oxidation of NADPH and shuttles electrons via its FAD and FMN cofactors to inactive MS-cob(II)alamin. A conserved aromatic resi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi2012228
更新日期：2011-12-27 00:00:00
abstract：:alpha-Conotoxin GI is a snail toxin protein consisting of 13 amino acids cross-linked by 2 intramolecular disulfide bridges. This toxin is an antagonist of acetylcholine receptors. The native sequence has been synthesized, along with nine additional variants in which non-cysteine residues are replaced by alanine or th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00111a021
更新日期：1991-11-26 00:00:00
abstract：:Retinol (vitamin A alcohol) is a hydrophobic compound and distributes in vivo mainly between binding proteins and cellular membranes. To better clarify the nature of the interactions of retinol with these phases which have a high affinity for it, the thermodynamic parameters of these interactions were studied. The tem...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00468a014
更新日期：1990-04-24 00:00:00
abstract：:Eicosanoids have been implicated in the regulation of arterial smooth muscle cell (SMC) cholesteryl ester (CE) metabolism. These eicosanoids, which include prostacyclin (PGI2), stimulate CE hydrolytic activities. High-density lipoproteins (HDL), which promote cholesterol efflux, also stimulate PGI2 production, suggest...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00459a033
更新日期：1990-02-20 00:00:00
abstract：:Mixed phospholipid systems of ether-linked 1,2-dihexadecylphosphatidylcholine (DHPC) and ester-linked 1,2-dipalmitoylphosphatidylcholine (DPPC) have been studied by differential scanning calorimetry and X-ray diffraction. At maximum hydration (60 wt % water), DHPC shows three reversible transitions: a main (chain melt...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00395a006
更新日期：1987-10-20 00:00:00
abstract：:A critical point of interaction between F(1) and F(0) in the bacterial F(1)F(0)-ATP synthase is formed by the alpha and delta subunits. Previous work has shown that the N-terminal domain (residues 3-105) of the delta subunit forms a 6 alpha-helix bundle [Wilkens, S., Dunn, S. D., Chandler, J., Dahlquist, F. W., and Ca...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0510678
更新日期：2005-09-06 00:00:00
abstract：:Despite recognition that the plasma membrane (PM) is comprised of lipid raft domains that are key organizing sites of multiple signaling pathways and other cell functions, limited information is available regarding the structure and function in sterol dynamics of these microdomains. To begin to resolve these issues, M...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0602720
更新日期：2006-10-03 00:00:00
abstract：:Induced fit has been postulated to be an important component of ligand interactions with proteins, including protein-DNA interactions. We imagined that the entropic cost of induced fit might be highly dependent on the local protein sequence context around critical contact residues. To investigate this question, we ana...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi960256a
更新日期：1996-06-25 00:00:00
abstract：:Soluble guanylate cyclase isolated from bovine and rat lung is a heterodimeric hemoprotein composed of alpha1 and beta1 subunits. The heme binding region has been localized to residues 1-385 of the beta1 subunit [beta1(1-385)], while the catalytic site(s) have been localized to the C-terminal region of sGC. There are ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi972686m
更新日期：1998-03-31 00:00:00
abstract：:The formation and role of arachidonic acid (AA) and its metabolites during gonadotropin releasing hormone- (GnRH-) induced gonadotropin secretion were investigated in primary cultures of rat pituitary cells. Prelabeled cells ([3H]AA) responded to GnRH challenge with increased formation (about 2-fold) of the leukotrien...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00139a004
更新日期：1992-06-23 00:00:00
abstract：:A large fraction of a constitutively synthesized polypeptide, comprising 5% of the total Escherichia coli protein, is released when plasmolysed cells are subjected to osmotic shock into ice-cold water. Since the protein is not liberated by the conversion of cells to spheroplasts, it is not a typical periplasmic protei...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00656a008
更新日期：1976-06-01 00:00:00
abstract：:The circulating protein transthyretin (TTR) can unfold, oligomerize, and form highly structured amyloid fibrils that are deposited in tissues, causing organ damage and disease. This pathogenic process is caused by a heritable TTR point mutation in cases of familial TTR-related amyloidosis or wild-type TTR in cases of ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi5011249
更新日期：2015-01-20 00:00:00
abstract：:Interaction of a mitochondria-specific anionic phospholipid, cardiolipin (CL), with an intermembrane protein, cytochrome c (cyt c), yields a peroxidase complex. During apoptosis, the complex induces accumulation of CL oxidation products that are essential for detachment of cyt c from the mitochondrial membrane, induct...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi801507s
更新日期：2008-12-23 00:00:00
abstract：:Glycinamide ribonucleotide transformylase, the first of the two formyl group transferases of de novo purine biosynthesis requiring 10-formyltetrahydrofolate, has been purified 1500-fold, nearly to homogeneity, from the murine lymphoma cell line L5178Y. Purification of the enzyme was facilitated by the use of a gelatin...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00327a008
更新日期：1985-03-12 00:00:00
