Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Degeneration of human male germ cells was analysed by means of light (LM) and transmission electron (TEM) microscopy. The frequency of degenerating cells was correlated with that of Fas-expressing germ cells in human testes with normal spermatogenesis (n = 10), complete early maturation arrest (EMA) (n = 10) or incomplete late maturation arrest (LMA; n = 10) of spermatogenesis. LM analysis of testis sections with normal spermatogenesis indicated that degenerating germ cells were localized in the adluminal compartment of the seminiferous epithelium. TEM showed that apoptotic cells were mostly primary spermatocytes and, to a lesser extent, round or early elongating spermatids. Apoptotic germ cells appeared to be eliminated either in the seminiferous lumen or by Sertoli cell phagocytosis. An increased number of degenerating cells was observed in testes with LMA as compared with normal testes and testes with EMA of spermatogenesis (P < 0.001, Wilcoxon's rank sum test). Comparison of these results with those obtained from immunohistochemistry experiments demonstrated a tight correlation between the number of apoptotic cells and the number of Fas-expressing germ cells (P = 0.001, Spearman's rank = 0.69). These findings suggest that altered meiotic and post-meiotic germ cell maturation might be associated with an up-regulation of Fas gene expression capable of triggering apoptotic elimination of defective germ cells.
Mol Hum Reprod 2002 Mar
PMID:Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis. 1187 Feb 28

The structure of a chromosomal extended-spectrum beta-lactamase (ESBL) having the ability to hydrolyze cephalosporins including cefuroxime and ceftazidime has been determined by X-ray crystallography to 1.75 A resolution. The species-specific class A beta-lactamase from Proteus vulgaris K1 was crystallized at pH 6.25 and its structure solved by molecular replacement. Refinement of the model resulted in crystallographic R and R(free) of 16.9 % and 19.3 %, respectively. The folding of the K1 enzyme is broadly similar to that of non-ESBL TEM-type beta-lactamases (2 A rmsd for C(alpha)) and differs by only 0.35 A for all atoms of six conserved residues in the catalytic site. Other residues promoting extended-spectrum activity in K1 include the side-chains of atypical residues Ser237 and Lys276. These side-chains are linked by two water molecules, one of which lies in the position normally filled by the guanidinium group of Arg244, present in most non-ESBL enzymes but absent from K1. The ammonium group of Lys276, ca 3.5 A from the virtual Arg244 guanidinium position, may interact with polar R2 substitutents on the dihydrothiazene ring of cephalosporins.
J Mol Biol 2002 Mar 15
PMID:Structure of an extended-spectrum class A beta-lactamase from Proteus vulgaris K1. 1191 82

Recently, Quintana and others published the results of TEM investigations of ferritin cores extracted from the brain tissue of patients suffering from progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). These ferrihydrite (fFe2O3.9H2O) cores from the iron storage protein ferritin were found to contain a ferrous (Fe2+) iron-bearing biomineral with cubic structure similar to the magnetite standards which were measured. This is a highly important result as magnetic and electron microscopy analysis has demonstrated the presence of magnetite (Fe3O4) and maghemite (gammaFe2O3) in human brain tissue.
Cell Mol Biol (Noisy-le-grand) 2001
PMID:On the structural form of iron in ferritin cores associated with progressive supranuclear palsy and Alzheimer's disease. 1087 42

Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the beta-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182-->Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.
J Mol Biol 2002 Jun 28
PMID:Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs. 1207 36

By mixing an aqueous solution of CuCl2 with an NaDC aqueous solution of various concentration and initial molar ratio, seven coordinated samples with distinct appearances and characters were obtained. Their structures and components were investigated by FT-IR spectroscopy, EXAFS (the extended X-ray absorption fine structure), thermal analysis, X-ray diffraction, laser light scattering, TEM (transmission electron micrograph), element analysis and ICP (inductively coupled plasma) analysis. The following conclusions were given: (1) The complexes of Cu2+-NaDC with distinct appearances and properties were synthesized. (2) After Cu(DC)2 dissolved in NaDC aqueous solution, larger micelles (30-90 nm diameter) formed in the supernate, it is a mixed micelle with Cu(DC)2 and NaDC. So these micelles are a new kind of micelle containing two kinds of metal ions. This is a new result using metal ions as bridges to form micelle. (3) According to the different concentration of Cu2+ to NaDC, the complexes formed as gel or poly-crystals. Both the composition of gel complexes and the coordination structure of carboxyl groups with metal ions varied with the initial molar ratio of Cu2+ to Na+. The gel complexes exhibits the non-stoichiometric character. (4) These results are in agreement with physiological condition. All the different states such as gel, precipitate, micelles of various structures are present in bile of gallbladder. We can suggest an ideal model of the interaction between Cu2+ and bile salts in vivo.
Spectrochim Acta A Mol Biomol Spectrosc 2002 May
PMID:The interaction of Cu2 + ions and NaDC micelles. 1208 72

We have previously reported on the IR spectra of styrene, acrylonitrile, and methyl methacrylate (known as the SAN co-polymer), as well as the glass transitions. Not too much work on the refractive indices has been performed, and the refractive indices for a variety of these mixtures and some selected TEM pictures will be presented in this note.
Spectrochim Acta A Mol Biomol Spectrosc 2002 Oct
PMID:Refractive indices for various co-polymer mixtures of styrene, acrylonitrile, and methyl methacrylate. 1239 47

A robust and fast DNA chip method was developed in order to detect the various beta-lactam antibiotic-resistance genes in one slide. These genes included PSE, OXA, FOX, MEN, CMY, TEM, SHV, OXY, and AmpC. beta-lactam antibiotic-resistance genes were labeled with a fluorescent nucleotide by a multiplex polymerase chain reaction using a mixture of specific primer sets for each gene. This labeled target was hybridized with a DNA chip that contained the spots of the specific probe DNAs for each beta-lactam antibiotic-resistance gene. This technique made it possible to detect the specific resistance gene, even in a single bacterium.
Mol Cells 2002 Oct 31
PMID:Development of DNA chip for the simultaneous detection of various beta-lactam antibiotic-resistant genes. 1244 90

The structural and functional development of the pulmonary system is dependent upon appropriate early vascularization of the embryonic lung. Our previous in vitro studies in a rat model indicated that insulin-like growth factor-I (IGF-I) is a potent angiogenic agent for fetal lung endothelial cells. To assess its role on human vascular lung development, we first examined the expression of IGF-I/II and IGF receptor type I (IGF-IR) in human embryonic and fetal lung tissues at 4-12 wk of gestation. Immunohistochemical and in situ hybridization studies revealed the presence of IGF-I/II-IGF-IR ligands and mRNA transcripts in embryonic lungs as early as 4 wk gestation. Immunotargeting using an anti-IGF-IR neutralizing antibody on human fetal lung explants demonstrated a significant blockade of IGF-IR signaling. Inactivation of IGF-IR resulted in a loss of endothelial cells, accompanied by dramatic changes in fetal lung explant morphology. Terminal transferase dUTP end-labeling assay and TEM studies of anti-IGF-IR-treated lungs demonstrated numerous apoptotic mesenchymal cells. Rat embryonic lung explant studies further validated the importance of the IGF-IGF-IR system for lung vascular development. These data provide the first demonstration of IGF-I/II expression in the human lung in early gestation and indicate that the IGF family of growth factors, acting through the IGF-IR, is required as a survival factor during normal human lung vascularization.
Am J Respir Cell Mol Biol 2003 Feb
PMID:Insulin-like growth factor-I receptor-mediated vasculogenesis/angiogenesis in human lung development. 1254 Apr 79

Bacterial beta-lactamases hydrolyze beta-lactam antibiotics such as penicillins and cephalosporins. The TEM-type class A beta-lactamase SHV-2 is a natural variant that exhibits activity against third-generation cephalosporins normally resistant to hydrolysis by class A enzymes. SHV-2 contains a single Gly238Ser change relative to the wild-type enzyme SHV-1. Crystallographic refinement of a model including hydrogen atoms gave R and R(free) of 12.4% and 15.0% for data to 0.91 A resolution. The hydrogen atom on the O(gamma) atom of the reactive Ser70 is clearly seen for the first time, bridging to the water molecule activated by Glu166. Though hydrogen atoms on the nearby Lys73 are not seen, this observation of the Ser70 hydrogen atom and the hydrogen bonding pattern around Lys73 indicate that Lys73 is protonated. These findings support a role for the Glu166-water couple, rather than Lys73, as the general base in the deprotonation of Ser70 in the acylation process of class A beta-lactamases. Overlay of SHV-2 with SHV-1 shows a significant 1-3 A displacement in the 238-242 beta-strand-turn segment, making the beta-lactam binding site more open to newer cephalosporins with large C7 substituents and thereby expanding the substrate spectrum of the variant enzyme. The OH group of the buried Ser238 side-chain hydrogen bonds to the main-chain CO of Asn170 on the Omega loop, that is unaltered in position relative to SHV-1. This structural role for Ser238 in protein-protein binding makes less likely its hydrogen bonding to oximino cephalosporins such as cefotaxime or ceftazidime.
J Mol Biol 2003 Apr 18
PMID:Ultrahigh resolution structure of a class A beta-lactamase: on the mechanism and specificity of the extended-spectrum SHV-2 enzyme. 1268 14

We have developed a simple and general method that allows for the facile recombination of distantly related (or unrelated) proteins at multiple discrete sites. To evaluate the sequence-independent site-directed chimeragenesis (SISDC) method, we have recombined beta-lactamases TEM-1 and PSE-4 at seven sites, examined the quality of the chimeric genes created, and screened the library of 2(8) (256) chimeras for functional enzymes. Probe hybridization and sequencing analyses revealed that SISDC generated a random library with little sequence bias and in which all targeted fragments were recombined in the desired order. Sequencing the genes from clones having functional lactamases identified 14 unique chimeras. These chimeras are characterized by a lower level of disruption, as calculated by the SCHEMA algorithm, than the library as a whole. These results illustrate the use of SISDC in creating designed chimeric protein libraries and further illustrate the ability of SCHEMA to identify chimeras whose folded structures are likely not to be disrupted by recombination.
J Mol Biol 2003 Jul 04
PMID:General method for sequence-independent site-directed chimeragenesis. 1282 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>