Abstract:
:In protein and RNA macromolecules, only a limited number of different side-chain chemical groups are available to function as catalysts. The myriad of enzyme-catalyzed reactions results from the ability of most of these groups to function either as nucleophilic, electrophilic, or general acid-base catalysts, and the key to their adapted chemical function lies in their states of protonation. Ionization is determined by the intrinsic pKa of the group and the microenvironment created around the group by the protein or RNA structure, which perturbs its intrinsic pKa to its functional or apparent pKa. These pKa shifts result from interactions of the catalytic group with other fully or partially charged groups as well as the polarity or dielectric of the medium that surrounds it. The electrostatic interactions between ionizable groups found on the surface of macromolecules are weak and cause only slight pKa perturbations (<2 units). The sum of many of these weak electrostatic interactions helps contribute to the stability of native or folded macromolecules and their ligand complexes. However, the pKa values of catalytic groups that are found in the active sites of numerous enzymes are significantly more perturbed (>2 units) and are the subject of this review. The magnitudes of these pKa perturbations are analyzed with respect to the structural details of the active-site microenvironment and the energetics of the reactions that they catalyze.
journal_name
IUBMB Lifejournal_title
IUBMB lifeauthors
Harris TK,Turner GJdoi
10.1080/15216540211468keywords:
subject
Has Abstractpub_date
2002-02-01 00:00:00pages
85-98issue
2eissn
1521-6543issn
1521-6551journal_volume
53pub_type
杂志文章,评审相关文献
IUBMB LIFE文献大全abstract::Changes in the status of DNA methylation are one of the most common molecular alterations in human neoplasia. We aimed to identify epigenetic molecular markers in serum for early detection of breast cancer. Authors analyzed retrospectively the methylation status of RARβ2 and APC genes in serum samples from 121 breast ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1346
更新日期:2015-01-01 00:00:00
abstract::Pilins or fimbrilins are a class of proteins found in bacterial surface pilus, a hair-like surface appendage. Both the Gram-negative and -positive bacteria produce pilins to assemble pili on their cell-surface for different purposes including adherence, twitching motility, conjugation, immunomodulation, biofilm format...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.1400
更新日期:2015-07-01 00:00:00
abstract::Heat shock proteins (Hsps) are a highly conserved family of proteins. The regulation of expression of Hsps in Mycobacterium tuberculosis, is regulated both positively and negatively by alternate sigma factors and transcriptional DNA repressors, respectively. HspR is a negative regulator of expression of hsps, DnaK, Cl...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1438
更新日期:2015-11-01 00:00:00
abstract::Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to ...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/1521654031000153012
更新日期:2003-06-01 00:00:00
abstract::Cancers have a clonal origin, yet their chromosomes and genes are non-clonal or heterogeneous due to an inherent genomic instability. However, the cause of this genomic instability is still debated. One theory postulates that mutations in genes that are involved in DNA repair and in chromosome segregation are the prim...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540410001667902
更新日期:2004-02-01 00:00:00
abstract::Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscular dystrophies. The isolation of the defective gene in DMD/BMD has led to a better understanding of the disease process and has promoted studies regarding the application of molecular therapy. The purpose of this review is to present the progress made...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540212333
更新日期:2002-03-01 00:00:00
abstract::Upregulation of haptoglobin (Hp) expression in the rat during the acute phase (AP) response is the result of synergistic effects of IL-6-, IL-1beta-, and corticosterone-activated signaling pathways. IL-6 signaling terminates in cis-trans interactions of the Hp gene hormone-responsive element (HRE) with transcription f...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.313
更新日期:2010-03-01 00:00:00
abstract::Nur77 is a member of nuclear receptor superfamily that acts as a transcription factor and regulates expression of multiple genes. Subcellular localization of Nur77 protein plays an important role in the survival and cell death. In this study, we have predicted and confirmed alternatively spliced two new transcripts of...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1605
更新日期:2017-02-01 00:00:00
abstract::Members of the GATA family of transcription factors play key roles in the differentiation of specific cell lineages by regulating the expression of target genes. Three GATA factors play distinct roles in hematopoietic differentiation. In order to better understand how these GATA factors function to regulate genes thro...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2195
更新日期:2020-01-01 00:00:00
abstract::Alkyl-dihydroxyacetonephosphate synthase (alkyl-DHAP synthase) is a peroxisomal enzyme that plays a key role in ether phospholipid biosynthesis. To determine the turnover of alkyl-DHAP synthase in several peroxisomal disorders, pulse-chase experiments were performed. In control fibroblasts, mature alkyl-DHAP synthase ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/713803571
更新日期:1999-12-01 00:00:00
abstract::The aggressive biological behavior of invasive and metastatic cancer is considered to be the most insidious and life-threatening aspect for breast cancer patients. It is mostly the result of changes in many molecular characteristics of tumor cells, including alterations in gene expression and the balance of proteolyti...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/15216540701395074
更新日期:2007-06-01 00:00:00
abstract::Immune infiltration of tumors has been increasingly accepted as a prognostic factor in colon cancer. Here, we aim to develop a novel immune signature, based on estimated immune landscape from tumor transcriptomes, to predict the overall survival of patients with colon cancer. The compositions of 22 immune cell subtype...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2124
更新日期:2019-11-01 00:00:00
abstract::Recently, three independent laboratories reported the generation of induced pluripotent stem cells (iPSCs) from pig (Sus scrofa). This finding sums to the growing list of species (mouse, human, monkey, and rat, in this order) for which successful reprogramming using exogenous factors has been achieved, and multiple ot...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.307
更新日期:2010-04-01 00:00:00
abstract::During the hand plate development, the processes of cell differentiation and control of cell death are relevant to ensure a correct shape of the limb. The progenitor cell pool that later will differentiate into cartilage to form the digits arises from undifferentiated mesenchymal cells beneath the apical ectodermal ri...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.563
更新日期:2011-10-01 00:00:00
abstract::Vibrio cholerae is the causative agent of the diarrheal disease cholera, for which biofilm communities are considered to be environmental reservoirs. In endemic regions, and after algal blooms, which may result from phosphate enrichment following agricultural runoff, the bacterium is released from biofilms resulting i...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2439
更新日期:2021-02-01 00:00:00
abstract::In this review we discuss the limited efficacy for current pharmacological agents used in prophylaxis and treatment of thrombosis and highlight targeted delivery of anti-thrombotic agents to fibrin, platelets, red blood cells and endothelium. ...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.474
更新日期:2011-08-01 00:00:00
abstract::Peroxynitrite is an inorganic toxin of physiological interest, formed from the diffusion-controlled reaction of superoxide and nitrogen monoxide with a rate constant of (1.6 +/- 0.3) x 10(10) M(-1) s(-1). On the basis of three experiments we conclude that homolysis of the O-O bond in peroxynitrous acid is unlikely: (1...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540310001628690
更新日期:2003-10-01 00:00:00
abstract::T cell (TC) activation requires the coordinated signaling of the T cell receptor (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR occupancy. Coreceptor molecules set the threshold for TC activation by controlling different regulatory signaling loops. The Cbl family members prevent undesi...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.554
更新日期:2011-10-01 00:00:00
abstract::Transfected human apoptosis signal-regulating kinase 1 (ASK1) produces a 150 kDa protein. However, we have detected endogenous ASK1 predominantly as 39 and 50 kDa C-terminal and 75 and 110 kDa N-terminal fragments in a panel of nontransfected cancer cell lines and HUVEC endothelial cells. This suggests that in nonapop...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.24
更新日期:2008-03-01 00:00:00
abstract::The immunosuppressant cyclosporin A (CsA)-sensitive nuclear factor of activated T cells 1 (NFAT1) has been known to be a transcriptional regulator of cytokine and viral genes during the immune response. By analyses of serial deletion, mutation, and heterologous promoter assay, we report here that the CsA-sensitive NFA...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/152165401753311807
更新日期:2001-04-01 00:00:00
abstract::In tsRSV-infected NRK (tsNRK) cells, pp60(v-src) reactivation by temperature-shift from a nonpermissive temperature, 39 C, to a permissive one, 32 degrees C, induced the production of inositol phosphates (IPt) and phosphatidylethanol (PEt). This was accompanied by an increase in membrane-associated protein kinase C (P...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/713803467
更新日期:1999-07-01 00:00:00
abstract::Magnetic targeting has shown promise to improve the efficacy and safety of different classes of therapeutic agents by enabling their active guidance to the site of disease and minimizing dissemination to nontarget tissues. However, its translation into clinic has proven difficult because of inherent limitations of tra...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.479
更新日期:2011-08-01 00:00:00
abstract::Over the years, microRNA-20b-3p (miR-20b-3p) has been found to play an essential role in human diseases; we aimed to investigate the effect of miR-20b-3p on the progression of diabetic retinopathy (DR). The DR rat models were established by streptozotocin injection and treated with miR-20b-3p mimics, silenced, or over...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2267
更新日期:2020-07-01 00:00:00
abstract::Nucleotides of transfer RNAs (tRNAs) are highly modified, particularly at the anticodon. Bacterial tRNAs that read A-ending codons are especially notable. The U34 nucleotide canonically present in these tRNAs is modified by a wide range of complex chemical constituents. An additional two A-ending codons are not read b...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2120
更新日期:2019-08-01 00:00:00
abstract::Triclosan, a well-known inhibitor of Enoyl Acyl Carrier Protein Reductase (ENR) from several pathogenic organisms, is a promising lead compound to design effective drugs. We have solved the X-ray crystal structures of Plasmodium falciparum ENR in complex with triclosan variants having different substituted and unsubst...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.327
更新日期:2010-06-01 00:00:00
abstract::Myocardial ischemia/reperfusion (I/R) injury greatly contributes to myocardial tissue damage in patients with coronary disease, which eventually leads to heart failure. Long noncoding RNAs (lncRNAs) have an emerging role in the process of myocardial I/R injury. Our previous work revealed the protective role of miR-374...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2428
更新日期:2020-12-09 00:00:00
abstract::The conformational stability of the homotetrameric Plasmodium falciparum beta-ketoacyl-ACP reductase (FabG) was determined by guanidinium chloride-induced isothermal and thermal denaturation. The reversible unfolding transitions were monitored by intrinsic fluorescence, circular dichroism (CD) spectroscopy and by meas...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/15216540701472113
更新日期:2007-07-01 00:00:00
abstract::For 8 years, it was not understood why certain genes of plant mitochondria contain CGG (arginine) codons at positions where tryptophan codons (UGG) are present in the corresponding genes of nonplant species. Identification and sequencing of a tRNA(Trp) gene showed that it is not able to decode the CGG codon. Analysis ...
journal_title:IUBMB life
pub_type: 历史文章,杂志文章,评审
doi:10.1002/iub.277
更新日期:2009-12-01 00:00:00
abstract::We have adapted the Java Molecular Viewer (JMV) to virtual reality display environments, through a number of extensions to the Java 3D code. Phylogenetic information derived from multiple alignments (temporal information) can be overlaid onto molecule structures (spatial information). The number of sequences included ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/1521654031000136255
更新日期:2003-04-01 00:00:00
abstract::1,25-Dihydroxyvitamin D3 [1,25(OH)2 D3 ] has recently been shown to have immunomodulatory property. This study aimed to investigate the expression and potential role of 1,25(OH)2 D3 in the pathogenesis of diabetic retinopathy (DR) in the Uygur population. Blood samples were obtained from 22 patients with proliferative...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1501
更新日期:2016-06-01 00:00:00