Abstract:
:Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme operating in the gluconeogenesis and glyceroneogenesis pathways. Previous work has demonstrated that the enzyme cycles between a catalytically inactive open state and a catalytically active closed state. The transition of the enzyme between these states requires the transition of several active site loops to shift from mobile, disordered structural elements to stable ordered states. The mechanism by which these disorder-order transitions are coupled to the ligation state of the active site however is not fully understood. To further investigate the mechanisms by which the mobility of the active site loops is coupled to enzymatic function and the transitioning of the enzyme between the two conformational states, we have conducted structural and functional studies of point mutants of E89. E89 is a proposed key member of the interaction network of mobile elements as it resides in the R-loop region of the enzyme active site. These new data demonstrate the importance of the R-loop in coordinating interactions between substrates at the OAA/PEP binding site and the mobile R- and Ω-loop domains. In turn, the studies more generally demonstrate the mechanisms by which the intrinsic ligand binding energy can be utilized in catalysis to drive unfavorable conformational changes, changes that are subsequently required for both optimal catalytic activity and fidelity.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Johnson TA,Mcleod MJ,Holyoak Tdoi
10.1021/acs.biochem.5b01215subject
Has Abstractpub_date
2016-01-26 00:00:00pages
575-87issue
3eissn
0006-2960issn
1520-4995journal_volume
55pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::13C NMR has been used to demonstrate the metabolism of dilute solutions of labeled formaldehyde by Escherichia coli to methanol, formate, carbon dioxide, and several other unidentified metabolites which contain labeled CH2 groups. Aeration of bacterial suspensions within the spectrometer dramatically increased the rat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00298a017
更新日期:1984-01-31 00:00:00
abstract::Phthalate dioxygenase from Pseudomonas cepacia contains a mononuclear ferrous center that is strictly required for catalytic oxygen activation. The spectroscopic characterization of this iron site and its ligand interactions has been complicated in the past by interference from a Rieske-type binuclear (2Fe-2S) cluster...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00069a017
更新日期:1993-05-11 00:00:00
abstract::Experimental measurements of the kinetic mechanism involving isoleucyl-tRNA synthetase proofreading valyl-tRNAIle in Escherichia coli have been incorporated into the conventional Michaelis-Menten model for this system. The model was subjected to a detailed mathematical analysis in the steady state. The results of this...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00303a019
更新日期:1984-04-10 00:00:00
abstract::Sensory rhodopsin I (SRI) is a seven-transmembrane helix retinylidene protein that mediates color-sensitive phototaxis responses through its bound transducer HtrI in the archaeon Halobacterium salinarum. Deprotonation of the Schiff base attachment site of the chromophore accompanies formation of the SRI signaling stat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991180w
更新日期:1999-10-05 00:00:00
abstract::Murine fibroblasts cultured in the presence of fibroblast growth factor-1 express relatively high levels of FR-1, a approximately 36 kDa protein related to the aldo-keto reductase superfamily [Donohue, P. J., Alberts, G. F., Hampton, B. S., Winkles, J. A. (1994) J. Biol. Chem. 269, 8604-8609]. While the crystal struct...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9804333
更新日期:1998-09-15 00:00:00
abstract::An X-ray structure analysis of a crystal of mutant Asp229----Ala of cyclodextrin glycosyltransferase from Bacillus circulans (Ec 2.4.1.19) that had been shortly exposed to beta-cyclodextrin showed density corresponding to a maltose bound at the catalytic center. The crystal structure was refined to an R-factor of 18.7...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00152a009
更新日期:1992-09-22 00:00:00
abstract::Phosphodeoxyribomutase from Escherichia coli has been purified to homogeneity. Chromatography on DEAE-Sephadex revealed three peaks of enzyme activity, designated form I, form II, and form III. Form III could be further separated into form III-1 and form III-2 by polyacrylamide gel electrophoresis. The four different ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00674a021
更新日期:1975-02-11 00:00:00
abstract::R67 dihydrofolate reductase (DHFR) is a type II DHFR produced by bacteria as a resistance mechanism to the increased clinical use of the antibacterial drug trimethoprim. Type II DHFRs are not homologous in either sequence or structure with chromosomal DHFRs. The type II enzymes contain four identical subunits which fo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0026425
更新日期:2001-04-10 00:00:00
abstract::Production of single-strand breaks (ssb) and double-strand breaks (dsb) of PM2 phage DNA by several structurally related bleomycin (BLM) analogues was studied by gel electrophoresis. BLM A2 and BLM B2 produced a comparable extent of dsb. In various experiments, BLM A2 and BLM B2, at 22-41 ng/mL, degraded 50% of the fo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00505a001
更新日期:1981-01-20 00:00:00
abstract::The spin equilibria of several derivatives of human methemoglobin were probed by resonance Raman scattering. The intensity of lines in the Raman spectrum gives a measure of the high-spin (S = 5/2) to low-spin (S = 1/2) ratio which agrees well with the spin equilibria determined from direct magnetic susceptibility meas...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00438a056
更新日期:1989-06-13 00:00:00
abstract::Three distinct fibrinolytic enzymes have been purified from the venom of Crotalus basiliscus basiliscus (the Mexican west coast rattlesnake). The high-performance liquid chromatography-based purification comprised the following steps: (a) hydrophobic interaction chromatography; (b) hydroxylapatite chromatography; (c) ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00134a003
更新日期:1992-05-19 00:00:00
abstract::In Saccharomyces cerevisiae, the histidine-containing phosphotransfer (HPt) protein YPD1 transfers phosphoryl groups between the three different response regulator domains of SLN1, SSK1, and SKN7 (designated R1, R2, and R3, respectively). Together these proteins form a branched histidine-aspartic acid phosphorelay sys...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048433s
更新日期:2005-01-11 00:00:00
abstract::The skeletal muscle Ca2+ release channel (RYR1) is regulated by calmodulin in both its Ca2+-free (apocalmodulin) and Ca2+-bound (Ca2+ calmodulin) states. Apocalmodulin is an activator of the channel, and Ca2+ calmodulin is an inhibitor of the channel. Both apocalmodulin and Ca2+ calmodulin binding sites on RYR1 are de...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9907431
更新日期:1999-06-29 00:00:00
abstract::Minibrain kinase/dual-specificity tyrosine phosphorylation regulated kinase 1A (MNB/DYRK1A) is a proline/arginine-directed serine/threonine kinase implicated in the learning deficits of Down syndrome. Epigallocatechin-3-gallate (EGCG), the major tea polyphenolic compound, is a potent MNB/DYRK1A inhibitor. In this stud...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060632j
更新日期:2006-10-03 00:00:00
abstract::Triple helix-forming oligonucleotides (TFOs) bind with high affinity and specificity to homopurine-homopyrimidine sequences in DNA and have been shown to inhibit transcription of target genes in various experimental systems. In the present study, we evaluated the ability of 3'-amino-modified phosphodiester TFOs direct...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi992185w
更新日期:2000-05-02 00:00:00
abstract::An important but poorly characterized contribution to the thermodynamics of protein-DNA interactions is the loss of entropy that occurs from restricting the conformational freedom of amino acid side chains. The effect of restricting the flexibility of several side chains at a protein-DNA interface may be comparable in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00195
更新日期:2018-05-15 00:00:00
abstract::The effect of opportunistic infections (OI) on immune-compromised populations has been known for decades, but the recent AIDS epidemic has sparked renewed interest in the development of new anti-OI agents. The mechanism of action of a series of cationic unfused-aromatic anti-OI drugs is believed to involve binding of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi971599r
更新日期:1997-12-09 00:00:00
abstract::The thermodynamic quantities of the anti-dinitrophenyl antibody-hapten interaction are reported for rabbit, goat, and guinea pig antibodies. Rabbit and goat antibodies had similar exothermic enthalpy changes for their reaction with 2,4-dinitrophenyl-L-lysine (-13.9 and -14.8 kcal/mol, respectively). The enthalpy chang...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00694a032
更新日期:1975-11-18 00:00:00
abstract::The dependence of the activity of bovine Cu,Zn superoxide dismutase on pH and ionic strength was extensively investigated in the ranges of pH 7.4-pH 12.3 and of ionic strength of 0.02-0.25 M. The results obtained indicate that two positively charged groups having pK values of approximately 10.1 and 10.8 are involved i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00385a043
更新日期:1987-06-02 00:00:00
abstract::In this report we provide biochemical evidence that a highly purified synaptic plasma membrane fraction derived from rat brain, after intraventricular injection of 35S-labeled sodium sulfate, is enriched in a number of large sulfated glycoproteins compared with a purified myelin fraction studied concurrently. A fracti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00670a005
更新日期:1976-12-14 00:00:00
abstract::We report the first experimental characterization of the full thermodynamic profile for binding of urea to a native protein. We measured the volumetric parameters of lysozyme at pH 7.0 as a function of urea within a temperature range of 18-45 °C. At neutral pH, lysozyme retains its native conformation between 0 and 8 ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00805
更新日期:2016-11-29 00:00:00
abstract::Changes in pH can alter the structure and activity of proteins and may be used by the cell to control molecular function. This coupling can also be used in non-native applications through the design of pH-sensitive biomolecules. For example, the pH (low) insertion peptide (pHLIP) can spontaneously insert into a lipid ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00380
更新日期:2016-08-09 00:00:00
abstract::MenB, the 1,4-dihydroxy-2-naphthoyl-CoA synthase from the bacterial menaquinone biosynthesis pathway, catalyzes an intramolecular Claisen condensation (Dieckmann reaction) in which the electrophile is an unactivated carboxylic acid. Mechanistic studies on this crotonase family member have been hindered by partial acti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200877x
更新日期:2011-11-08 00:00:00
abstract::Glutaminase (GLS1/2) catalyzes the conversion of L-glutamine to L-glutamate and ammonia. The level of a splice variant of GLS1 (GAC) is elevated in certain cancers, and GAC is specifically inhibited by bis-2-(5-phenylacetimido-1,2,4,thiadiazol-2-yl)ethyl sulfide (BPTES). We report here the first full-length crystal st...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi201613d
更新日期:2011-12-20 00:00:00
abstract::Recent crystal structures of the small ribosomal subunit have made it possible to examine the detailed energetics of codon recognition on the ribosome by computational methods. The binding of cognate and near-cognate anticodon stem loops to the ribosome decoding center, with mRNA containing the Phe UUU and UUC codons,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061713i
更新日期:2007-01-09 00:00:00
abstract::The 600-MHz proton spectrum of dethiobiotin (prepared from d-biotin with Raney nickel) was measured in order to gain information pertaining to its stereochemical homogeneity. The spectrum demonstrated clearly that the material is a 6:1 mixture of two stereoisomers. The cis compound, corresponding to the stereochemistr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00307a002
更新日期:1984-06-05 00:00:00
abstract::Escherichia coli asparagine synthetase B (AS-B) catalyzes the synthesis of asparagine from aspartate, glutamine, and ATP. A combination of kinetic, isotopic-labeling, and stoichiometry studies have been performed to define the nature of nitrogen transfer mediated by AS-B. The results of initial rate studies were consi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981058h
更新日期:1998-09-22 00:00:00
abstract::Arachidonate metabolites are potent biological mediators affecting multiple cellular functions. Although prostaglandins of the E series, which are products of the cyclooxygenase pathway, have been known as inhibitors or down-regulators of fibroblast proliferation and collagen synthesis, the more recently discovered pr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00408a028
更新日期:1988-04-19 00:00:00
abstract::Laser light scattering has been applied to a systematic study of a heterogeneous solution of tubulin at low temperature--conditions under which tubulin assembly into microtubules does not take place. Methods of analyzing laser light scattering results obtained from solutions containing multiple components are discusse...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00645a020
更新日期:1977-12-27 00:00:00
abstract::The organization and interaction of chlorophylls (Chl) and the kinetics of the energy transfer in the core antenna of photosystem I (PSI) trimeric and monomeric complexes, isolated from Spirulina platensis with Triton X-100 have been studied by stationary and time-resolved fluorescence. At 295 K both complexes show an...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970386z
更新日期:1997-11-11 00:00:00