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

Monoclonal antibodies against rabbit metallothioneins (MT) were prepared by in vitro immunization of mouse lymphocytes with a mixture of the two forms of metallothionein MT1 and MT2. Six IgM antibodies (TN1,3,4,5,6,7) which bind to metallothionein were characterized. Antibody TN3 is specific for rabbit MT1 and does not react with any other MT's tested. TN5 is specific for both rabbit MT1 and MT2. TN7 is specific for rabbit MT2 but not MT1 and cross-reacts also with Chinese hamster, mouse and rat metallothioneins. The antibodies TN1, TN4 and TN6 bind not only to rabbit MT1 and MT2 but also to other metal binding proteins like alcohol dehydrogenase and carbonic anhydrase.
Mol Immunol 1986 Oct
PMID:Monoclonal antibodies against metallothioneins and metalloproteins. 379 22

A quantitative structure-activity relationship (QSAR) (log K = 1.55 alpha + 0.64 log P - 2.07I1 - 3.28I2 + 6.94) has been formulated for the binding of a set of substituted benzenesulfonamides to human carbonic anhydrase. The binding constant (K) are from the studies of King and Burgen [Proc. R. Soc. Lond. B. 193:107-125 (1976)], sigma is the Hammett electronic substituent constant, P is the octanol/water partition coefficient, and I1 and I2 are indicator variables for meta and ortho substituents, respectively. The negative coefficients with the indicator variables suggest steric hindrance by these substituents in contrast to para substituents. Qualitative features of the QSAR are correlated with a color stereomolecular graphics model of the enzyme-inhibitor complex which was constructed from the X-ray crystallographic coordinates of the enzyme.
Mol Pharmacol 1985 May
PMID:A quantitative structure-activity relationship and molecular graphics study of carbonic anhydrase inhibitors. 399 Jun 76

The study of internal mobility in enzymes is of considerable importance for the understanding of their catalytic function, which cannot be adequately described as a property of a rigid protein. [13C]NMR spectroscopy permits simultaneous and selective observation of spectral lines from carbon atoms in many different residues in the enzyme with the chemical shift and relaxation parameters sensitive to structure, conformation and local motion. The changes in internal mobility in bovine carbonic anhydrase B (carbonate hydrolase, EC 4.2.1.1) in the native form and at various stages of denaturation are studied. Measurements of the relaxation parameters (T1, T1 rho) and of the NOE of 13C nuclei in the native protein showed that the extensive beta-sheet together with groups in the active center has a considerable internal librational mobility with tau G about 10(-11) s. This librational mobility is fairly uniform for all the alpha-carbons in the native enzyme. The use of a semiempirical modification of the motional theory proposed by Woessner allows to use simultaneously all the relaxation parameters measured in order to determine reliable values of the various correlation times.
Mol Biol (Mosk)
PMID:[Study of bovine carbonic anhydrase by 13C-NMR-spectroscopy]. 641 Jan 81

The 250 MHz 1H-NMR spectrum of horse carbonic anhydrase I (or B) (carbonate hydro-lyase, EC 4.2.1.1) was measured as a function of pH under various conditions. Eight resonances corresponding to histidine C-2 protons and four resonances corresponding to histidine C-4 protons were identified and assigned to individual histidine residues in the enzyme molecule. Substantial similarities between horse and human carbonic anhydrases I were demonstrated. While the human enzyme has three titratable histidine residues in its active site, the horse enzyme has only two, His-67 in the human enzyme being replaced by Gln in the horse enzyme (Jabusch, J.R., Bray, R.P. and Deutsch, H.F. (1980) J. Biol. Chem. 255, 9196-9204). This substitution has small but significant effects on the behaviour of the other active-site histidines. His-64 and His-200. However, His-64 has an anomalously low pKa value also in horse isoenzyme I, as previously observed in human isoenzyme I (Campbell, I.D., Lindskog, S. and White, A.I. (1974) J. Mol. Biol. 90, 469-489).
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PMID:Proton nuclear magnetic resonance studies of histidines in horse carbonic anhydrase I. 641 19

Pulmonary carbonic anhydrase (CA) activity plays important roles in carbon dioxide exchange, fluid secretion, and pH regulation. This study reports the use of molecular and immunologic techniques to characterize expression of the high-activity cytosolic isoenzyme CA II in rat lung tissue. Northern blot analysis of RNA isolated from various rat tissues revealed that the lung is a site of abundant tissue-specific CA II gene expression. The cell type primarily responsible for CA II expression in the lung was identified by immunohistochemistry as the alveolar type II pneumocyte. RNA blot and immunoblot analyses of isolated rat type II cells in culture confirmed CA II expression by this cell type. Little immunoreactive CA I and no CA IV was detected in these cells. Inhibition studies confirmed that the majority of CA activity in isolated type II cells is attributable to CA II. CA II expression was found to continue in these cells beyond 72 h in culture, a timeframe during which these cells had dedifferentiated. The ontologic pattern of CA II expression in the lung was found by RNA blot analysis to be disparate from that of the surfactant-associated proteins. These observations suggest roles for CA II in alveolar pneumocytes independent of (or in addition to) participation in surfactant biology. Such roles may include the regulation of fluid secretion or facilitation of carbon dioxide elimination.
Am J Respir Cell Mol Biol 1994 May
PMID:Carbonic anhydrase II expression in rat type II pneumocytes. 751 10

Two distinct cDNA clones encoding carbonic anhydrase (CA) were isolated from an Arabidopsis thaliana lambda YES library. One of these clones, CA1, encodes a 36.1-kD polypeptide and is essentially the same as a previously reported Arabidopsis CA cDNA (C.A. Raines, P.R. Horsnell, C. Holder, J.C. Lloyd [1992] Plant Mol Biol 20: 1143-1148). Comparison of the derived amino acid sequence from this clone with other plant CAs suggests the presence of a chloroplastic transit peptide, which, when cleaved, would render a mature protein of 24.3 kD. The other identified clone, CA2, encodes a 28.3-kD polypeptide, which in addition to other residue changes, is 78 amino acids shorter at the N terminus than the primary product of CA1. The two cDNAs exhibit 76.9% sequence similarity at the DNA level and 84.6% identity between the predicted amino acid sequences. A polyclonal antibody generated against pea CA (N. Majeau, J.R. Coleman [1991] Plant Physiol 100: 1077-1078) hybridized to two protein bands (25 and 28 kD) from a total leaf extract and to only one band (25 kD) from a chloroplastic protein extract. The data suggest that the CA2 protein is an extrachloroplastic form of CA, presumably localized in the cytoplasm. Southern analysis indicated that CA1 and CA2 are encoded by different genes. Northern analysis of total leaf RNA resulted in hybridization of CA1- and CA2-derived probes to two transcripts of 1.47 and 1.2 kb, respectively. These data provide additional evidence that the CA2 clone is a full-length cDNA and that two transcribed CA genes are present in the Arabidopsis genome. Transcript levels of CA1 and CA2 decreased 70 and 20%, respectively, when mature plants were transferred to dark for 24 h. Seedlings germinated in the dark showed CA1 and CA2 transcript abundance levels of 4 and 22%, respectively, when compared with light-germinated seedlings. These data suggest that expression of CA1 is light regulated and dependent of leaf and/or chloroplast development. A possible role for cytoplasmic CA in the plant cell is discussed.
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PMID:Characterization and expression of two cDNAs encoding carbonic anhydrase in Arabidopsis thaliana. 752 May 89

We report the effect of temperature on the equilibrium dissociation constants (Kl) for a series of six sulfonamides binding to three carbonic anhydrase (CA) isoenzymes (I, II, and IV). Kl values obtained at 0 degree, 15 degrees, and 23 degrees under conditions of nearly constant and low substrate (CO2) concentration were used to calculate enthalpy and entropy changes associated with sulfonamide binding as well as to provide estimates of inhibitory potency of sulfonamides at 37 degrees. We studies four classic sulfonamide (methazolamide, benzolamide, ethoxzolamide, and sulfanilamide) and the novel sulfonamides MK-507 (dorzolamide) and CF3SO2NH2. In all cases, the Kl was observed to increase with increasing temperature, which is consistent with a negative enthalpy of sulfonamide binding. The extrapolated increase in Kl over the 0-37 degrees temperature range varied from 4-fold for sulfanilamide binding to CA l to 14-fold for CF3SO2NH2 binding to CA IV, corresponding to binding enthalpy values of -7.2 to -11.7 kcal/mol. For CA II and I, entropy changes associated with sulfonamide binding were in general modest and ranged from -5.3 to +4.1 entropy units (eu) for five of the compounds tested. In contrast, ethoxzolamide binding was associated with a relatively large positive entropy change. Also, the variatione in k(on) and k(off) with temperature were studied for three sulfonamides binding to CA II. The association rate constants for methazolamide, benzolamide, and ethoxzolamide binding showed increases of 2-fold or less, whereas dissociation constants increased 3-9-fold over the range of 0-37 degrees. Thus, the temperature effect in increasing Kl is in large part due to a faster rate of sulfonamide dissociation. Apparent activation parameters at 23 degrees for k(on) were delta H++ = -2.35 to 3.8 kcal/mol, delta G++ = 7.3 to 8.6 kcal/mol, and delta S++ = -16.2 to -32.7 entropy units. For k(off), the corresponding values were delta H++ = 5.6 to 14.5 kcal/mol, delta G++ = 19.0 kcal/mol, and delta S++ = -14.8 to -45.7 entropy units.
Mol Pharmacol 1995 Sep
PMID:The effect of temperature on the binding of sulfonamides to carbonic anhydrase isoenzymes I, II, and IV. 756 29

The periplasmic carbonic anhydrase (CA) gene CAH1 of Chlamydomonas reinhardtii codes for a highly processed secreted glycoprotein. The primary translation product of the CAH1 gene is targeted to the ER, where it is proteolytically processed to yield two different subunits, glycosylated, assembled into an active heterotetramer, and secreted. After replacing the target leader sequence with that from tobacco anionic peroxidase, expression of this gene in transgenic tobacco plants was investigated. SDS-PAGE gels of the purified protein from tobacco, showed that it migrated as a series of discrete bands (two large and one small) with slightly faster mobility than the comparable bands in the purified algal protein. The expressed protein in the plant was active, and staining with thymol and sulfuric acid confirmed that it was also glycosylated. The periplasmic CA1 (peri-CA1) also was found to be enriched in the intercellular fluid of transgenic tobacco, indicating it was secreted. The specific activity of the enzyme and its sensitivity to sulfonamide inhibitors were similar to that of the native algal enzyme. These results suggest that the post translational processing of Chlamydomonas peri-CA1 is largely conserved in a higher plant.
Plant Mol Biol 1995 Oct
PMID:Post-translational processing of the highly processed, secreted periplasmic carbonic anhydrase of Chlamydomonas is largely conserved in transgenic tobacco. 757 81

During the evolution of C4 plants from C3 plants, both the function and intracellular location of carbonic anhydrase (CA) have changed. To determine whether these changes are due to changes at the molecular level, we have studied the cDNA sequences and the expression of CA from Flaveria species demonstrating different photosynthetic pathways. In leaf extracts from F. bidentis (C4), F. brownii (C4-like), F. linearis (C3-C4) and F. pringlei (C3), two polypeptides of M(r) 31 kDa and 35 kDa cross-reacted with anti-spinach CA antibodies. However, the relative labelling intensities of the two polypeptides differed depending on the species. Northern blot analysis indicated at least two CA transcripts are present in each Flaveria species with sizes ranging from 1.1 to 1.6 kb. Carbonic anhydrase cDNAs from all four Flaveria species studied encode an open reading frame for a polypeptide of 35-36 kDa. The amino acid sequences deduced from all four Flaveria cDNAs share at least 70% homology with the sequences of other dicot CAs. The F. bidentis (C4) CA sequence was found to be the least similar of the Flaveria proteins and, as most of the sequence dissimilarity was found in the first third of the CA molecule, these differences may be involved in the intracellular targeting of CA. A neighbour-joining tree inferred from CA amino acid sequences showed that the Flaveria CAs cluster with other dicot CAs forming a group distinct from those of monocot CAs and prokaryotic and Chlamydomonas periplasmic CAs.
Plant Mol Biol 1995 Oct
PMID:Molecular comparison of carbonic anhydrase from Flaveria species demonstrating different photosynthetic pathways. 757 85

The present investigation shows a possible correlation between serum zinc level and peptic ulcer disease/syndrome and a plausible mechanism for the finding. Clinicopathological study of patients with peptic ulcer diseases followed by confirmed endoscopic findings shows a significant low serum zinc level, 0.846 +/- 0.15 ug/ ml +/- S.D. (P < 0.001) with an exception of approx. 10% of the patients. To understand the cellular mechanism of low zinc levels in serum, tissue zinc content of gastric mucosa was determined. A significant increased value (P < 0.01) of zinc content in gastric mucosa of patients with peptic ulcer diathesis was noted. Carbonic anhydrase, a major zinc containing enzyme was also determined in erythrocytes. However, no change of erythrocyte carbonic anhydrase content was noted. To assess the nutritional status of the patients in relation to the low serum zinc value, serum albumin level was also determined. The low serum zinc level of the peptic ulcer patients is possibly due to the positive shift for the zinc from serum to the gastric mucosa.
Biochem Mol Biol Int 1995 Aug
PMID:Serum zinc level : a possible index in the pathogenesis of peptic ulcer syndrome. 758 Oct 13


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