Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complete amino acid sequence of the alpha chain of histidine decarboxylase of Lactobacillus 30a has been established by isolation and analysis of the eight methionine-containing tryptic peptides of this chain. These peptides provide the overlaps required to order all nine peptides derived by complete cyanogen bromide cleavage of the alpha chain (Huynh, Q.K., Vaaler, G.L., Recsei, P.A., and Snell, E.E. (1984) J. Biol. Chem. 259, 2826-2832). Ordering of six of the latter peptides was confirmed by isolation and analysis of four peptides derived by incomplete cyanogen bromide cleavage. The alpha chain is composed of 226 residues and has a molecular weight of 24,892 calculated from the sequence. These results and the previously determined sequence of the beta chain (Vaaler, G.L., Recsei, P.A., Fox, J.L., and Snell, E.E. (1982) J. Biol. Chem. 257, 12770-12774) establish the complete amino acid sequence of the enzyme and of the pi chain of prohistidine decarboxylase. The latter is composed of 307 amino acids and has a calculated molecular weight of 33,731. Four segments of the pi chain sequence are repeated. The bond between Ser-81 and Ser-82 that is cleaved during proenzyme activation is in an uncharged portion of the sequence that is rich in serine and threonine residues and is predicted to be part of a beta sheet structure.
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PMID:Histidine decarboxylase of Lactobacillus 30a. Sequences of the overlapping peptides, the complete alpha chain, and prohistidine decarboxylase. 669 97

Secretion of platelet granule constituents is closely associated with the phosphorylation of a cytosol polypeptide of Mr = 47,000 that we have called P47 (Haslam, R. J., Lynham, J. A., and Fox, J. E. B. (1979) Biochem. J. 178, 397-406). This polypeptide is a substrate of Ca2+-activated phospholipid-dependent protein kinase (Kawahara, Y., Takai, Y., Minakuchi, R., Sano, K., and Nishizuka, Y. (1980) Biochem. Biophys. Res. Commun. 97, 309-317). Two-dimensional gel electrophoresis of protein from human platelets that had been preincubated with 32Pi demonstrated the presence under control conditions of 2-3 major forms of P47 that contained very little 32P (pI values, 6.6-6.8) and, after induction of secretion with thrombin, their replacement by 7-9 highly labeled phosphorylated forms of P47 (pI values, 6.1-6.5). Native phosphorylated P47 was purified from thrombin-stimulated 32P-labeled platelets by ammonium sulfate fractionation and column chromatography on DEAE-cellulose, phenyl-Sepharose, and hydroxylapatite. The final 32P-labeled product was obtained in a yield of 20-25% and was purified about 400-fold relative to platelet lysate. This material was homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis but, like the starting material, contained 7-9 separable phosphorylated components with different pI values. Purified phosphorylated P47 had a sedimentation coefficient (s20,w) of 3.57 S and a Stokes radius of 3.33 nm from which an Mr = 49,000 and a frictional ratio (f/f0) of 1.4 were calculated. These findings and failure to detect multimers after treatment of the protein with dimethyl suberimidate indicate that P47 normally exists as a monomer. The 32P-labeled phosphate present in purified P47 had the chemical stability of serine or threonine phosphoesters and analysis indicated the presence of 83% phosphoserine and 17% phosphothreonine. Limited proteolysis of purified 32P-labeled P47 by Staphylococcus aureus V8 protease generated a major unlabeled fragment (Mr = 23,500) and up to six labeled fragments (Mr = 24,700-14,800), the relative amounts of the latter depending on the extent of proteolysis. The same labeled fragments were obtained after proteolysis of each of the major phosphorylated components of P47, suggesting that these represent different phosphorylation states of variants of the same protein and that most or all of the phosphorylation sites are on a single 14,800-Da segment of the protein. The availability of pure native phosphorylated P47 should facilitate investigation of the physiological role of this protein in platelets.
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PMID:Purification and characterization of the 47,000-dalton protein phosphorylated during degranulation of human platelets. 688 23

Infection by hepatitis C viruses (HCVs) is a serious medical problem with no broadly effective treatment available for the progression of chronic hepatitis. The catalytic activity of a viral serine protease located in the N-terminal one-third of nonstructural protein 3 (NS3) is required for polyprotein processing at four site-specific junctions. The three-dimensional crystal structure of the NS3-NS4A co-complex [Kim, J. L., Morgenstern, K. A., Lin, C., Fox, T., Dwyer, M. D., Landro, J. A., Chambers, S. P., Markland, W., Lepre, C. A., O'Malley, E. T., Harbeson, S. L., Rice, C. M., Murcko, M. A., Caron, P. R., & Thomson, J. A. (1996) Cell 87, 343-355] delineates a small hydrophobic region within the 54-residue NS4A protein that intercalates with and makes extensive contacts to the core of the protease. The current investigation addresses the mechanism of NS3 protease catalytic activation by NS4A utilizing a small synthetic NS4A peptide (residues 1678-1691 of the virus polyprotein sequence) and the recombinantly expressed protease domain of NS3. The addition of NS4A dramatically increased NS3 kcat and kcat/Km catalytic parameters when measured against small peptide substrates representing the different site-specific junctions of the polyprotein. The catalytic effect of natural and non-natural amino acid substitutions at the P1 position in a 5A/5B peptide substrate was investigated. NS3-NS4A demonstrated a marked catalytic preference for the cysteine residue commonly found in authentic substrates. The pH dependence of the NS3 hydrolysis reaction is not affected by the presence of NS4A. This result suggests that NS4A does not change the pKa values of the active site residues of NS3 protease. A steady state kinetic analysis was performed and indicated that the binding of NS4A and the peptide substrate occurs in an ordered fashion during the catalytic cycle, with NS4A binding first. Two distinct kinetic classes of peptidyl inhibitors based upon the 5A/5B cleavage site were identified. An NS4A-independent class is devoid of prime residues. A second class of inhibitors is NS4A-dependent and contains a natural or non-natural cyclic amino acid substituted for the commonly found P1' residue serine. These inhibitors display an up to 80-fold increase in affinity for NS3 protease in the presence of NS4A. Sequential truncation of prime and P residues from this inhibitor class demonstrated the fact that the P4' and P1' residues are crucial for potent inhibition. The selectivity of this NS4A effect is interpreted using a model of the 5A/5B decapeptide substrate bound to the active site of the NS3-NS4A structure.
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PMID:Mechanistic role of an NS4A peptide cofactor with the truncated NS3 protease of hepatitis C virus: elucidation of the NS4A stimulatory effect via kinetic analysis and inhibitor mapping. 923 76

Transcription factors of the Fox (fork head box) family are involved in cellular specification and determination processes. Here, we report on the isolation and first characterisation of two members of the FoxO subclass in Xenopus laevis, xFoxO1 and xFoxO3. These sequences exhibit 68% (67%) and 69% (70%) identity to their mouse (human) orthologues, respectively. Serine and threonine residues, which are phosphorylated upon insulin signalling, are evolutionarily conserved from frogs to mammals. xFoxO1 and xFoxO3 genes are maternally transcribed, but transcripts disappear during early cleavage stages. Zygotic transcription of both genes starts at the late neurula stages and transcripts accumulate at the end of organogenesis. While maternal transcripts of both genes are found within the animal half of the early embryo, zygotic transcripts show distinct patterns. xFoxO1 expression is observed in the pronephros, within head mesenchyme in front of the eye, within the branchial arches and in the liver primordium. At the late neurula, xFoxO3 is found to be specifically expressed in the anterior neural plate and in neural crest cells. Later, expression of xFoxO3 is observed in a variety of organs and tissues, like the head, the branchial arches and the somites.
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PMID:The FoxO-subclass in Xenopus laevis development. 1556 14

Trifluoromethyl group containing oxazolidines (Fox) are conveniently synthesized by condensation of serine esters with trifluoroacetaldehyde hemiacetal or trifluoroacetone. These oxazolidines can undergo N-acylation and amidification reactions and are completely configurationally and hydrolytically stable. Therefore, they can be considered as highly valuable proline surrogates (Tfm-pseudoprolines).
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PMID:Synthesis of 2-trifluoromethyl-1,3-oxazolidines as hydrolytically stable pseudoprolines. 2048 51