Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TrJ14 is a cytotoxic human IgG1 lambda hybridoma mAb that recognized a novel HLA-A epitope expressed by lymphoblastoid B cells that are homo- or heterozygous for A2, A3, A11, A30, A31, A33, A68 and A69. Based on these results, the HLA type of cell line TEM (10w9057) was retyped as A66. When peripheral blood T cells isolated freshly from 265 HLA-typed normal individuals served as targets, TrJ14 killed cells expressing two TrJ14-positive HLA-A alleles, as well as the majority of cells having one TrJ14-positive and one TrJ14-negative HLA-A antigen. However, TrJ14 failed to recognize or reacted weakly with most HLA-A2 and -A3 heterozygous normal T cells when A2 or A3 was coexpressed together with a TrJ14-negative antigen. The serological reactivity of TrJ14 correlated with the amino acid valine and aspartic acid at positions 76 and 77 of the alpha 1-domain helix. These amino acids were shared exclusively by all the identified TrJ14+ alleles.
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PMID:A novel HLA-A determinant recognized by a cytotoxic human hybridoma IgG1 monoclonal antibody (TrJ14). 753 38

TEM-35 (inhibitor resistant TEM (IRT)-4) and TEM-36 (IRT-7) clavulanic acid-resistant beta-lactamases have evolved from TEM-1 beta-lactamase by two substitutions: a methionine to a leucine or a valine at position 69 and an asparagine to an aspartic acid at position 276. The substitutions at position 69 have previously been shown to be responsible for the resistance to clavulanic acid, and they are the only mutations encountered in TEM-33 (IRT-5) and TEM-34 (IRT-6). However, the N276D substitution has never been found alone in inhibitor-resistant beta-lactamases, and its role in resistance to clavulanic acid was thus unclear. The N276D mutant was constructed, purified, and kinetically characterized. It was shown that the substitution has a direct effect on substrate affinities and leads to slightly decreased catalytic efficiencies and that clavulanic acid becomes a poor substrate of the enzyme. Electrospray mass spectrometry demonstrated the simultaneous presence of free and inhibited enzymes after incubation with clavulanic acid and showed that a cleaved moiety of clavulanic acid leads to the formation of the major inactive complex. The kinetic properties of the N276D mutant could be linked to a salt-bridge interaction of aspartic acid 276 with arginine 244 that alters the electrostatic properties in the substrate binding area.
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PMID:The asparagine to aspartic acid substitution at position 276 of TEM-35 and TEM-36 is involved in the beta-lactamase resistance to clavulanic acid. 762 42

In SHV-type beta-actamases, position 276 (in Ambler's numbering scheme) is occupied by an asparagine (Asn) residue. The effect on SHV-1 beta-lactamase and its extended-spectrum derivative SHV-5 of substituting an aspartic acid (Asp) residue for Asn276 was studied. Mutations were introduced by a PCR-based site-directed mutagenesis procedure. Wild-type SHV-1 and -5 beta-lactamases and their respective Asn276-->Asp mutants were expressed under isogenic conditions by cloning the respective bla genes into the pBCSK(+) plasmid and transforming Escherichia coli DH5alpha. Determination of IC50 showed that SHV-1(Asn276-->Asp), compared with SHV-1, was inhibited by 8- and 8.8-fold higher concentrations of clavulanate and tazobactam respectively. Replacement of Asn276 by Asp in SHV-5 beta-lactamase caused a ten-fold increase in the IC50 of clavulanate; the increases in the IC50s of tazobactam and sulbactam were 10- and 5.5-fold, respectively. Beta-lactam susceptibility testing showed that both Asn276-->Asp mutant enzymes, compared with the parental beta-lactamases, conferred slightly lower levels of resistance to penicillins (amoxycillin, ticarcillin and piperacillin), cephalosporins (cephalothin and cefprozil) and some of the expanded-spectrum oxyimino beta-lactams tested (cefotaxime, ceftriaxone and aztreonam). The MICs of ceftazidime remained unaltered, while those of cefepime and cefpirome were slightly elevated in the clones producing the mutant beta-lactamases. The latter clones were also less susceptible to penicillin-inhibitor combinations. Asn276-->Asp mutation was associated with changes in the substrate profiles of SHV-1 and SHV-5 enzymes. Based on the structure of TEM-1 beta-lactamase, the potential effects of the introduced mutation on SHV-1 and SHV-5 are discussed.
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PMID:Aspartic acid for asparagine substitution at position 276 reduces susceptibility to mechanism-based inhibitors in SHV-1 and SHV-5 beta-lactamases. 1038 Oct 97

The treatment of infectious diseases by beta-lactam antibiotics is continuously challenged by the emergence and dissemination of new beta-lactamases. In most cases, the cephalosporinase activity of class A enzymes results from a few mutations in the TEM and SHV penicillinases. The PER-1 beta-lactamase was characterized as a class A enzyme displaying a cephalosporinase activity. This activity was, however, insensitive to the mutations of residues known to be critical for providing extended substrate profiles to TEM and SHV. The x-ray structure of the protein, solved at 1.9-A resolution, reveals that two of the most conserved features in class A beta-lactamases are not present in this enzyme: the fold of the Omega-loop and the cis conformation of the peptide bond between residues 166 and 167. The new fold of the Omega-loop and the insertion of four residues at the edge of strand S3 generate a broad cavity that may easily accommodate the bulky substituents of cephalosporin substrates. The trans conformation of the 166-167 bond is related to the presence of an aspartic acid at position 136. Selection of class A enzymes based on the occurrence of both Asp(136) and Asn(179) identifies a subgroup of enzymes with high sequence homology.
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PMID:The high resolution crystal structure for class A beta-lactamase PER-1 reveals the bases for its increase in breadth of activity. 1082 76

During mollusk shell formation, the mineral phase forms within an organic matrix composed of beta-chitin, silk-like proteins, and acidic glycoproteins rich in aspartic acid. The matrix is widely assumed to play an important role in controlling mineralization. Thus, understanding its structure is of prime importance. Cryo-transmission electron microscopy (Cryo-TEM) studies of the matrix of the bivalve Atrina embedded in vitrified ice show that the interlamellar sheets are composed mainly of highly ordered and aligned beta-chitin fibrils. The silk, which is quantitatively an important component of the matrix, could not be imaged within the sheets. Organic material was, however, observed between sheets. We infer that this is the location of the silk. As this material reveals no regular structure, we suggest that at least prior to mineralization the silk is in the form of a hydrated gel. This is supported by cryo-TEM structural observations of an artificial assembly of beta-chitin with and without silk. This view of the nacreous organic matrix significantly changes previous models of the matrix structure and hence hypotheses pertaining to the mechanisms by which mineral formation occurs.
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PMID:Structure of the nacreous organic matrix of a bivalve mollusk shell examined in the hydrated state using cryo-TEM. 1156 61

The class A beta-lactamases and the transpeptidase domain of the penicillin-binding proteins (PBPs) share the same topology and conserved active-site residues. They both react with beta-lactams to form acylenzymes. The stability of the PBP acylenzymes results in the inhibition of the transpeptidase function and the antibiotic activity of the beta-lactams. In contrast, the deacylation of the beta-lactamases is extremely fast, resulting in a high turnover of beta-lactam hydrolysis, which confers resistance to these antibiotics. In TEM-1 beta-lactamase from Escherichia coli, Glu166 is required for the fast deacylation and occupies the same spatial location as Phe450 in PBP2x from Streptococcus pneumoniae. To gain insight into the deacylation mechanism of both enzymes, Phe450 of PBP2x was replaced by various residues. The introduction of ionizable side chains increased the deacylation rate, in a pH-dependent manner, for the acidic residues. The aspartic acid-containing variant had a 110-fold faster deacylation at pH 8. The magnitude of this effect is similar to that observed in a naturally occurring variant of PBP2x, which confers increased resistance to cephalosporins.
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PMID:Increase of the deacylation rate of PBP2x from Streptococcus pneumoniae by single point mutations mimicking the class A beta-lactamases. 1189 38

The acidic amino acid, such as aspartic acid (l-Asp), and glutamic acid are the primary active molecules of the glycoprotein on the organic/inorganic interface of biomineralized tissue. In this study, aspartic acid was used as the organic template in inducing the nucleation and growth of calcium carbonate. With the analysis of X-ray diffraction we investigated the relationship between the l-Asp concentration and the precipitation phase crystal structure of calcium carbonate. SEM and TEM were employed in the analysis of the morphological characteristic of the precipitation and the aggregation of the nanoscale porous phase. In order to get the direct evidence of the interaction between Ca2+ and l-Asp, the technique of QCM was used in the investigation of the coordinate interaction of Ca2+/l-Asp. As the results have shown, l-Asp alone is adequate to switch the transformation between calcite and vaterite, and neither soluble organic additions nor metal ions are needed. Meanwhile, the morphology, size and aggregative way of the deposition are also mediated with change of l-Asp concentration. To interpret the cause of the hierarchic structure range from nanoscale to micron-scale and the formation of the porous spheres of vaterite, an assumption of limited-fusion was proposed from the view of the small biomolecules polarity that can control over the growth of the crystals and the aggregation of the micro crystals. The conclusion also provide a new material synthesize strategy.
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PMID:Control over the crystal phase, shape, size and aggregation of calcium carbonate via a L-aspartic acid inducing process. 1502 Jan 69

The direct synthesis of hydroxyapatite-poly-L-aspartic acid (HA-PASP) nanocrystals has been carried out in presence of increasing amounts of PASP in solution up to 56 mmol/l. WAXS, TEM, TGA, IR and chemical analyses were used to characterize the structure, morphology and composition of the products. PASP is quantitatively incorporated into HA crystals, provoking a reduction of the coherent length of the crystalline domains. Furthermore, composite crystals display a greater length/width ratio with respect to the control HA crystals, and show a remarkable trend towards aggregation. The broadening of the X-ray diffraction reflections indicate a reduction of the coherent length along the long dimension 002 and the cross section 310 of the apatite crystals. The comparison between the morphological and structural data allows to suggest a specific interaction between PASP and HA structure.
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PMID:Nanocrystalline hydroxyapatite-polyaspartate composites. 1547 4

The OXA-1 beta-lactamase is one of the few class D enzymes that has an aspartate residue at position 66, a position that is proximal to the active-site residue Ser(67). In class A beta-lactamases, such as TEM-1 and SHV-1, residues adjacent to the active-site serine residue play a crucial role in inhibitor resistance and substrate selectivity. To probe the role of Asp(66) in substrate affinity and catalysis, we performed site-saturation mutagenesis at this position. Ampicillin MIC (minimum inhibitory concentration) values for the full set of Asp(66) mutants expressed in Escherichia coli DH10B ranged from < or =8 microg/ml for cysteine, proline and the basic amino acids to > or =256 microg/ml for asparagine, leucine and the wild-type aspartate. Replacement of aspartic acid by asparagine at position 66 also led to a moderate enhancement of extended-spectrum cephalosporin resistance. OXA-1 shares with other class D enzymes a carboxylated residue, Lys(70), that acts as a general base in the catalytic mechanism. The addition of 25 mM bicarbonate to Luria-Bertani-broth agar resulted in a > or =16-fold increase in MICs for most OXA-1 variants with amino acid replacements at position 66 when expressed in E. coli. Because Asp(66) forms hydrogen bonds with several other residues in the OXA-1 active site, we propose that this residue plays a role in stabilizing the CO2 bound to Lys(70) and thereby profoundly affects substrate turnover.
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PMID:The role of OXA-1 beta-lactamase Asp(66) in the stabilization of the active-site carbamate group and in substrate turnover. 1803 Dec 91

A block copolymer poly(2-ethyl-2-oxazoline)-block-poly(aspartic acid) (PEOz-b-PAsp) was synthesized and investigated as the carrier of antifungal drug amphotericin B (AmB). Polyion complex (PIC) micelles with clear core-shell structures were identified by TEM, which revealed that the PAsp segment became hydrophobic after it interacted with AmB. PEOz-b-PAsp increased not only the solubility of AmB but also simultaneously the drug potency. The prolonged release of AmB from micelles effectively inhibited the growth of Candida albicans even after three days of administration. Moreover, the in vitro cytotoxicity of AmB-loaded micelles was less than that of Fungizone, which is a powerful antifungal antibiotic that is adopted to treat various fungal infections. The PEOz-b-PAsp PIC micelles with lower cytotoxicity and higher potency than Fungizone represent a potential means of encapsulating basic/amphoteric drugs.
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PMID:Development of polyion complex micelles for encapsulating and delivering amphotericin B. 1929 11


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