Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five cationic porphyrins bearing one to four -N(CH(3))(3)(+) groups linked to the p-phenyl positions of 5,10,15,20-tetraphenylporphyrin (TPP) were synthesized in order to study the effect of overall charge and its distribution on the cellular uptake, phototoxicity and intracellular localization using human carcinoma HEp2 cells. The di-cationic porphyrins DADP-o and DADP-a accumulated the most within cells and preferentially localize within vesicular compartments and in mitochondria. Of these two only DADP-a was phototoxic to the cells (IC(50)=3 microM at 1 J/cm(2)). The mono-cationic porphyrin MAP was found to be the most phototoxic of the series, and it localized mainly in lipid membranes, including the plasma membrane, ER, mitochondria, and Golgi. Both the tri-cationic porphyrin TRAP and the tetra-cationic porphyrin TEAP localized subcellularly mainly in the mitochondria, but of the two only TEAP showed moderate phototoxicity (IC(50)=8 microM at 1 J/cm(2)). Our results suggest that MAP is the most promising PDT photosensitizer, and that both DADP-o and TRAP might find application as transport vehicles for therapeutics into cells.
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PMID:Effect of overall charge and charge distribution on cellular uptake, distribution and phototoxicity of cationic porphyrins in HEp2 cells. 2055 79

Photodamage to the endoplasmic reticulum (ER) can initiate a death pathway termed paraptosis. The "canonical" model of paraptosis, initiated by certain drugs and other stimuli, requires a brief interval of protein synthesis, involves the action of MAP kinases and can be followed by biochemical markers. The latter include changes in expression of AIP-1/Alix and IGF-1R proteins and translocation of HMGB-1 from nucleus to plasma membrane. There is also a report indicating that an enhanced level of autophagy can impair death by paraptosis. The pathway to paraptosis follows the canonical pathway when ER photodamage is minor (<LD50 ). When the extent of ER photodamage approaches LD90 levels, there are deviations from the "canonical" pathway: interfering with protein synthesis does not prevent paraptosis nor does a brief chilling of cells after irradiation, MAP kinases are not involved, and stimulation of autophagy was not cytoprotective. We had previously speculated that ER protein cross-linking might potentiate paraptosis (Photochem. Photobiol. 95, 2019, 1239) but this appears to be incorrect. At higher PDT doses, substantial cross-linking of a typical ER protein (BiP, binding immunoglobin protein, an HSP chaperone) was detected and paraptosis was impaired. This may relate to decreased mobility of cross-linked proteins. Other pathways to cell death were then observed.
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PMID:Paraptosis and Photodynamic Therapy: A Progress Report. 3211 10

Protein remote homology detection and protein fold recognition are two important tasks in protein structure and function prediction. There are three kinds of methods in this field, including the discriminative methods, the alignment methods, and the ranking methods. In this study, a new discriminative method called ReFold-MAP is proposed. The proposed method extracts comprehensive features based on three profile-based features: Motif-PSSM, ACC-PSSM, and PDT-profile. We call these features as MAP features, which incorporate the structural motif kernel information, the evolutionary information, and the sequence information. The experiments prove that ReFold-MAP outperforms other approaches. Therefore, ReFold-MAP will be a useful tool for protein remote homology detection and fold recognition.
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PMID:ReFold-MAP: Protein remote homology detection and fold recognition based on features extracted from profiles. 3316 Sep 6