Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wild-type human butyrylcholinesterase (BuChE) and Glu-197-->Asp and Asp-70-->Gly mutants (E197D and D70G respectively) were inhibited by di-isopropyl phosphorofluoridate under standard conditions of pH, temperature and pressure. The effect of hydrostatic and osmotic pressures on the aging process (dealkylation of an isopropyl chain) of phosphorylated enzymes [di-isopropylated (DIP)-BuChE] was investigated. Hydrostatic pressure markedly increased the rate of aging of wild-type enzyme. The average activation volume (DeltaV( not equal)) for the dealkylation reaction was -170 ml/mol for DIP wild-type BuChE. On the other hand, hydrostatic pressure had little effect on the aging of the DIP mutants (DeltaV( not equal)=-2.6 ml/mol for E197D and -2 ml/mol for D70G), suggesting that the transition state of the aging process was associated with an extended hydration and conformational change in wild-type BuChE, but not in the mutants. The rate of aging of wild-type and mutant enzymes decreased with osmotic pressure, allowing very large positive osmotic activation volumes (DeltaV not equal osm) to be estimated, thus probing the participation of water in the aging process. Molecular dynamics simulations performed on the active-site gorge of the wild-type DIP adduct showed that the isopropyl chain involved in aging was highly solvated, supporting the idea that water is important for stabilizing the transition state of the dealkylation reaction. Wild-type BuChE was inhibited by soman (pinacolyl methylphosphonofluoridate). Electrophoresis performed under high pressure [up to 2.5 kbar (1 bar=10(5) Pa)] showed that the soman-aged enzyme did not pass through a pressure-induced, molten-globule transition, unlike the native wild-type enzyme. Likewise, this transition was not seen for the native E197D and D70G mutants, indicating that these mutants are resistant to the penetration of water into their structure. The stability energetics of native and soman-aged wild-type BuChE were determined by differential scanning calorimetry. The pH-dependence of the midpoint transition temperature of endotherms indicated that the high difference in stabilization energy between aged and native BuChE (DeltaDeltaG=23.7 kJ/mol at pH 8.0) is mainly due to the salt bridge between protonated His-438 and PO(-), with pK(His-438)=8.3. A molecular dynamics simulation on the MIP adduct showed that there is no water molecule around the ion pair. The 'hydrostatic versus osmotic pressure' approach probed the importance of water in aging, and also revealed that Asp-70 and Glu-197 are the major residues controlling both the dynamics and the structural organization of the water/hydrogen-bond network in the active-site gorge of BuChE. In wild-type BuChE both residues function like valves, whereas in the mutant enzymes the water network is slack, and residues Gly-70 and Asp-197 function like check valves, i.e. forced penetration of water into the gorge is not easily achieved, thereby facilitating the release of water.
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PMID:Hydration change during the aging of phosphorylated human butyrylcholinesterase: importance of residues aspartate-70 and glutamate-197 in the water network as probed by hydrostatic and osmotic pressures. 1051 Mar 1

MIP channels occur in all classes of organism ranging from bacteria to man. There are two major categories of MIP channels, aquaporins and glycerol facilitators, which facilitate the diffusion across biological membranes of water or glycerol and other uncharged compounds, respectively. As a result of their involvement in osmoregulation and metabolism, MIP channels are believed to affect a wide range of biological processes.
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PMID:Microbial MIP channels. 1070 60

Human inherited cataract is both clinically diverse and genetically heterogeneous. Here we report the identification of the first mutations affecting the major intrinsic protein of the lens, MIP, encoded by the gene MIP on 12q14. MIP is a member of the aquaporin family of membrane-bound water channels. The mutations identified are predicted to disturb water flux across the lens cell membrane.
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PMID:Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q. 1080 46

The lens major intrinsic protein (MIP, AQP0) is known to function as a water and solute channel. However, MIP has also been reported to occur in close membrane contacts between lens fiber cells, indicating that it has adhesive properties in addition to its channel function. Using atomic force and cryo-electron microscopy we document that crystalline sheets reconstituted from purified ovine lens MIP mostly consisted of two layers. MIP lattices in the apposing membranes were in precise register, and determination of the membrane sidedness demonstrated that MIP molecules bound to each other via their extracellular surfaces. The surface structure of the latter was resolved to 0.61 nm and revealed two protruding domains providing a tight "tongue-and-groove" fit between apposing MIP molecules. Cryo-electron crystallography produced a projection map at 0.69 nm resolution with a mirror symmetry axis at 45 degrees to the lattice which was consistent with the double-layered nature of the reconstituted sheets. These data strongly suggest an adhesive function of MIP, and strengthen the view that MIP serves dual roles in the lens.
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PMID:Surface tongue-and-groove contours on lens MIP facilitate cell-to-cell adherence. 1089 Dec 68

Aquaporins are members of a large family of pore-forming intrinsic membrane proteins, the MIP family. Based on their permeability properties they are now further subdivided into aquaporins, with real water-selective pores, and aquaglyceroporins with slightly less selective pores. Aquaporins are expressed in a large variety of tissues throughout the body but in most situations it is not clear whether their presence is necessary for the proper physiological function of these tissues. This review focuses on recent insight into the physiological relevance of aquaporins gained from studying aquaporin knockout mouse models and from diseases, on new surprising findings related to gating and selectivity, and on the consequences of tetramerization for routing and the genetics of nephrogenic diabetes insipidus. The active fluid transport in proximal tubules and in salivary glands is seriously compromised by aquaporin deletion. This is in contrast to lung, airways and stomach, where active fluid transport proceeds unhindered in the face of greatly reduced water permeabilities due to aquaporin deletion. Therefore, aquaporins seem to be a necessity at extreme high rates of active fluid transport but appear to be more of a luxury at medium or low fluid transport rates.
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PMID:Phsyiological relevance of aquaporins: luxury or necessity? 1095 35

Two molecularly imprinted polymers were synthesized using either dichloromethane or toluene as the porogen and terbuthylazine as the template and were used as solid-phase extraction cartridges for the enrichment of six chlorotriazines (deisopropylatrazine, deethylatrazine, simazine, atrazine, propazine, and terbuthylazine) in natural water and sediment samples. The extracted samples were analyzed by liquid chromatography/diode array detection (LC/DAD). Several washing solvents, as well as different volumes, were tested for their ability to remove the matrix components nonspecifically adsorbed on the sorbents. This cleanup step was shown to be of prime importance to the successful extraction of the pesticides from the aqueous samples. The optimal analytical conditions were obtained when the MIP imprinted using dichloromethane was the sorbent, 2 mL of dichloromethane was used in the washing step, and the preconcentrated analytes were eluted with 8 mL of methanol. The recoveries were higher than 80% for all the chlorotriazines except for propazine (53%) when 50- or 100-mL groundwater samples, spiked at 1 microg/L level, were analyzed. The limits of detection varied from 0.05 to 0.2 microg/L when preconcentrating a 100-mL groundwater sample. Natural sediment samples from the Ebre Delta area (Tarragona, Spain) containing atrazine and deethylatrazine were Soxhlet extracted and analyzed by the methodology developed in this work. No significant interferences from the sample matrix were noticed, thus indicating good selectivity of the MIP sorbents used.
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PMID:Selective trace enrichment of chlorotriazine pesticides from natural waters and sediment samples using terbuthylazine molecularly imprinted polymers 1095 85

To establish a sensitive, accurate, and precise determination of arsenic compounds, a high power nitrogen microwave-induced plasma (1.3 kW) mass spectrometer (N2-MIP-MS) has been successfully coupled with an ultrasonic nebulizer (HPLC-USN) that is attached to a high-performance liquid chromatograph. It is examined as an element-specific detector for its applicability to the optimization and determination of seven arsenic compounds [arsenic acid, methylarsonic acid (MA), dimethylarsinic acid (DMA), arsenobetaine (AB), arsenocholine (AC), trimethylarsine oxide (TMAO), and tetramethylarsonium ion (CMI)]. This HPLC-USN-MIP-MS coupling is an encouraging combination as an alternative method for mass spectroscopy for elemental speciation analysis. Interchanging of the MIP-MS fabricated nebulizer (concentric) with an ultrasonic nebulizer, increases 3-6 times the ion signals for the anionic and 6-12 times those for the cationic arsenic compounds as compared to traditional methods. The HPLC-USN-MIP-MS combination used is excellent, amplifying the ion signals about 1.5-2 times for cationic and 1.3-2.8 times for the anionic arsenic compounds as compared to the HPLC-ICPMS coupling. The detection limits for As(V), MA, DMA, AB, TMAO, AC, and TMI (in Milli-Q-water) obtained with the optimized HPLC-USN-N2-MIP-MS system are 0.46, 0.36, 0.73, 0.21, 3.64, 0.39, and 0.32 microg L(-1), respectively, about 13-50 times lower than the HPLC-MIP-MS and about 3-11 times lower than the HPLC-ICPMS. The detection limits of As(V), MA, DMA, AB, TMAO, AC, and TMI, which spike in the urine, are deteriorated by 1.7-4.2 times compared with the detection limits of the seven different As compounds, which are prepared in the Milli-Q-water. The repeatability (RSD for three successive analyses) and reproducibility (RSD for three successive analyses performed on three different days), considering peak area and peak height, achieved for seven different arsenic compounds are 0.5-7 and 0.7-8%, comparable with the HPLC-ICPMS (0.3-8.5%; 4-12%) and HPLC-MIP-MS (0.4-9%; 5-12%) systems. The combined HPLC-USN-N2-MIP-MS has been adequately applied to the determination of AB in NIES Candidate Human Urine CRM. The results agree with the HPLC-ICPMS values. Chloride interference as 40Ar35Cl+ is not found in the urine and with the high chloride matrix (10000 mg L(-1)).
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PMID:Determination of arsenic compounds by high-performance liquid chromatography-ultrasonic nebulizer-high power nitrogen-microwave-induced plasma mass spectrometry: an accepted coupling. 1100 76

The gene for a new bacterial aquaporin, AqpX, was cloned from the pathogenic Gram-negative bacterium Brucella abortus. The gene was mapped on the large chromosome of B. abortus. It is flanked by one upstream and two downstream copies of the Brucella repeated sequence Bru-RS. Prediction from the nucleotide sequence indicated that the protein is a member of the MIP family, which comprises channels for water and/or solute transport. Expression in Xenopus oocytes and cryoelectron microscopy of Escherichia coli cells transformed with the aqpX gene confirmed that the protein is an efficient water channel. Glycerol uptake experiments in E. coli also showed that the protein is not able to transport glycerol.
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PMID:A functional water channel protein in the pathogenic bacterium Brucella abortus. 1110 83

In the present study we observed that the Haemophilus influenzae type b (Hib) porin, among the different surface bacterial components, is involved in the pathophysiology of bacterial meningitis. This study demonstrates that inoculation of Hib porin into the fourth cerebral ventricle causes the simultaneous expression of interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNF-alpha), and macrophage inflammatory protein 2 (MIP-2) at 6 h after inoculation. At 24 h, the expression of MIP-2 decreases while the expression of IL-1alpha and TNF-alpha increases. The mRNA expression of IL-1alpha, TNF-alpha, and MIP-2 is correlated with injury to the blood-brain barrier as demonstrated by the appearance of serum proteins and leukocytes in cerebrospinal fluid and by the increase in brain water content.
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PMID:Haemophilus influenzae porin contributes to signaling of the inflammatory cascade in rat brain. 1111 9

The detection of methylmercury species (MeHg) in fish tissue was investigated. Samples were digested with KOH-methanol and acidified prior to extraction with methylene chloride. MeHg was back-extracted from the organic phase into water. An aliquot of this aqueous solution (buffered to pH 5) was subjected to derivatization with sodium tetraphenylborate (NaBPh4) and then extracted with toluene. The organic phase containing MePhHg was injected into a gas chromatograph (GC) which is on-line with a microwave-induced plasma atomic emission spectrometer (MIP-AED). The quantification limit was about 0.6 microg/g and 0.1 microg/g of MeHg (as Hg) for 0.08 g of freeze-dried fish powder and 0.5 g of fresh samples, respectively. Two certified reference materials, CRM 464 (tuna fish) from Community Bureau of Reference-BCR and DORM-2 (dogfish muscle) from National Research Council Canada-NRC were selected for checking the accuracy of the method. This methodology was applied to the determination of MeHg in some kinds of fish from the Carmo river with alluvial gold recovery activities ("garimpos") in Mariana, Minas Gerais, Brazil.
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PMID:Determination of methylmercury in fish tissue by gas chromatography with microwave-induced plasma atomic emission spectrometry after derivatization with sodium tetraphenylborate. 1122 Mar 40


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