Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50502 (Hip)
 7,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both quantitative and qualitative chemical function based pharmacophore models of endothelin-A (ET(A)) selective receptor antagonists were generated by using the two algorithms HypoGen and HipHop, respectively, which are implemented in the Catalyst molecular modeling software. The input for HypoGen is a training set of 18 ET(A) antagonists exhibiting IC(50) values ranging between 0.19 nM and 67 microM. The best output hypothesis consists of five features: two hydrophobic (HY), one ring aromatic (RA), one hydrogen bond acceptor (HBA), and one negative ionizable (NI) function. The highest scoring Hip Hop model consists of six features: three hydrophobic (HY), one ring aromatic (RA), one hydrogen bond acceptor (HBA), and one negative ionizable (NI). It is the result of an input of three highly active, selective, and structurally diverse ET(A) antagonists. The predictive power of the quantitative model could be approved by using a test set of 30 compounds, whose activity values spread over 6 orders of magnitude. The two pharmacophores were tested according to their ability to extract known endothelin antagonists from the 3D molecular structure database of Derwent's World Drug Index. Thereby the main part of selective ET(A) antagonistic entries was detected by the two hypotheses. Furthermore, the pharmacophores were used to screen the Maybridge database. Six compounds were chosen from the output hit lists for in vitro testing of their ability to displace endothelin-1 from its receptor. Two of these are new potential lead compounds because they are structurally novel and exhibit satisfactory activity in the binding assay.
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PMID:Chemical function based pharmacophore generation of endothelin-A selective receptor antagonists. 1513 53

The high-affinity ligand-binding form of unactivated steroid receptors exists as a multicomponent complex that includes heat shock protein (Hsp)90; one of the immunophilins cyclophilin 40 (CyP40), FKBP51, or FKBP52; and an additional p23 protein component. Assembly of this heterocomplex is mediated by Hsp70 in association with accessory chaperones Hsp40, Hip, and Hop. A conserved structural element incorporating a tetratricopeptide repeat (TPR) domain mediates the interaction of the immunophilins with Hsp90 by accommodating the C-terminal EEVD peptide of the chaperone through a network of electrostatic and hydrophobic interactions. TPR cochaperones recognize the EEVD structural motif common to both Hsp90 and Hsp70 through a highly conserved clamp domain. In the present study, we investigated in vitro the molecular interactions between CyP40 and FKBP52 and other stress-related components involved in steroid receptor assembly, namely Hsp70 and Hop. Using a binding protein-retention assay with CyP40 fused to glutathione S-transferase immobilized on glutathione-agarose, we have identified the constitutively expressed form of Hsp70, heat shock cognate (Hsc)70, as an additional target for CyP40. Deletion mapping studies showed the binding determinants to be similar to those for CyP40-Hsp90 interaction. Furthermore, a mutational analysis of CyP40 clamp domain residues confirmed the importance of this motif in CyP40-Hsc70 interaction. Additional residues thought to mediate binding specificity through hydrophobic interactions were also important for Hsc70 recognition. CyP40 was shown to have a preference for Hsp90 over Hsc70. Surprisingly, FKBP52 was unable to compete with CyP40 for Hsc70 binding, suggesting that FKBP52 discriminates between the TPR cochaperone-binding sites in Hsp90 and Hsp70. Hop, which contains multiple units of the TPR motif, was shown to be a direct competitor with CyP40 for Hsc70 binding. Similar to Hop, CyP40 was shown not to influence the adenosine triphosphatase activity of Hsc70. Our results suggest that CyP40 may have a modulating role in Hsc70 as well as Hsp90 cellular function.
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PMID:Interaction of the Hsp90 cochaperone cyclophilin 40 with Hsc70. 1549 3

Heat-shock protein 90 (HSP90) has diverse functions in mammalian cells. It acts as molecular chaperone, together with several co-chaperone molecules (such as Hop, Hip, p23, cdc37, Aha, and immunophilins). HSP90 binds to its client proteins (such as steroid receptors, AKT, Bcr-Abl, Apaf-1, survivin, cyclin dependent kinases which are involved in signal transduction that regulate cell cycle, survival, and death, and promote their proper protein folding, assembly, and transportation across different cellular compartments. Failure of Hsp90 chaperone activity leads to misfolding of client proteins, which leads to ubiquitination and proteasome degradation, and this deregulating cellular homeostasis. Since tumor cells frequently overexpress the active form of HSP90, which is more susceptible to inhibition by small molecules such as geldanamycin and its analogs, HSP90 became an attractive target for cancer therapy. This paper will review the recent advances in HSP90-biology and will discuss the emerging role of the HSP90 inhibitors such as 17-allylamino-17 demethoxy-geldanamycin and other HSP-90-directed small molecules in cancer therapy.
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PMID:Heat-shock protein 90 inhibitors in cancer therapy: 17AAG and beyond. 1655 99

Three components of the chloroplast protein translocon, Tic110, Hsp93 (ClpC), and Tic40, have been shown to be important for protein translocation across the inner envelope membrane into the stroma. We show the molecular interactions among these three components that facilitate processing and translocation of precursor proteins. Transit-peptide binding by Tic110 recruits Tic40 binding to Tic110, which in turn causes the release of transit peptides from Tic110, freeing the transit peptides for processing. The Tic40 C-terminal domain, which is homologous to the C terminus of cochaperones Sti1p/Hop and Hip but with no known function, stimulates adenosine triphosphate hydrolysis by Hsp93. Hsp93 dissociates from Tic40 in the presence of adenosine diphosphate, suggesting that Tic40 functions as an adenosine triphosphatase activation protein for Hsp93. Our data suggest that chloroplasts have evolved the Tic40 cochaperone to increase the efficiency of precursor processing and translocation.
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PMID:Stimulation of transit-peptide release and ATP hydrolysis by a cochaperone during protein import into chloroplasts. 1715 58

Hip-Hop culture is a key social medium through which many young men and women from communities of colour in the USA construct their gender. In this study, we focused on the Hip-Hop club scene in New York City with the intention of unpacking narratives of gender dynamics from the perspective of young men and women, and how these relate to their sexual experiences. We conducted a three-year ethnographic study that included ethnographic observations of Hip-Hop clubs and their social scene, and in-depth interviews with young men and young women aged 15-21. This paper describes how young people negotiate gender relations on the dance floor of Hip-Hop clubs. The Hip-Hop club scene represents a context or setting where young men's masculinities are contested by the social environment, where women challenge hypermasculine privilege and where young people can set the stage for what happens next in their sexual and emotional interactions. Hip-Hop culture therefore provides a window into the gender and sexual scripts of many urban minority youth. A fuller understanding of these patterns can offer key insights into the social construction of sexual risk, as well as the possibilities for sexual health promotion, among young people in urban minority populations.
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PMID:The Hip-Hop club scene: Gender, grinding and sex. 1796

Retrospective dream components endorsed on the KJP Dream Inventory were correlated with those on the Short Test of Musical Preference for 68 graduate students in counseling psychology (11 men). Among 40 correlations, 6 were significant between preferences for Heavy Metal and Dissociative avoidance dreams (.32), Dreaming that you are dreaming (.40), Dreaming that you have fallen unconscious or asleep (.41), Recurring pleasantness (.31), and Awakening abruptly from a dream (-.31); between preferences for Rap/Hip-Hop and Sexual dreams (.27); and between preferences for Jazz and Recurring pleasantness in dreams (.33). Subjects preferring Classical music reported a higher incidence of Dreams of flying (.33) and rated higher Discontentedness in dreams (-.26). The meaning of these low values awaits research based on personality inventories and full dream reports.
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PMID:Retrospective dream components and musical preferences. 1898 41

In view of the nonavailability of complete X-ray structure of carbamates cocrystallized with AChE enzyme, the 3D-QSAR model development based on cocrystallized conformer (CCBA) as well as docked conformer-based alignment (DCBA) is not feasible. Therefore, the only two alternatives viz. pharmacophore and maximum common substructure-based alignments are left for the 3D-QSAR comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analyses (CoMSIA) model development. So, in the present study, the 3D-QSAR models have been developed using both alignment methods, where CoMFA and CoMSIA models based on pharmacophore-based alignment were in good agreement with each other and demonstrated significant superiority over MCS-based alignment in terms of leave-one-out (LOO) cross-validated q(2) values of 0.573 and 0.723 and the r(2) values of 0.972 and 0.950, respectively. The validation of the best CoMFA and CoMSIA models based on pharmacophore (Hip-Hop)-based alignment on a test set of 17 compounds provided significant predictive r(2) [r(2)(pred(test))] of 0.614 and 0.788, respectively. The contour map analyses revealed the relative importance of steric, electrostatic, and hydrophobicity for AChE inhibition activity. However, hydrophobic factor plays a major contribution to the AChE inhibitory activity modulation which is in strong agreement with the fact that the AChE is having a wide active site gorge (approximately 20 A) occupied by a large number of hydrophobic amino acid residues.
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PMID:Consensus superiority of the pharmacophore-based alignment, over maximum common substructure (MCS): 3D-QSAR studies on carbamates as acetylcholinesterase inhibitors. 1944 65

The platelet surface is a dynamic interface that changes rapidly in response to stimuli to co-ordinate the formation of thrombi at sites of vascular injury. Tight control is essential as loss of organisation may result in the inappropriate formation of thrombi (thrombosis) or excessive bleeding. In this paper we describe the comparative analysis of resting and thrombin-stimulated platelet membrane proteomes and associated proteins to identify proteins important to platelet function. Surface proteins were labelled using a biotin tag and isolated by NeurtrAvidin affinity chromatography. Liquid phase IEF and SDS-PAGE were used to separate proteins, and bands of increased intensity in the stimulated platelet fractions were digested and identified by FT-ICR mass spectrometry. Novel proteins were identified along with proteins known to be translocated to the platelet surface. Furthermore, many platelet proteins revealed changes in location associated with function, including G6B and Hip-55. HIP-55 is an SH3-binding protein important in T-cell receptor signalling. Further analysis of HIP-55 revealed that this adaptor protein becomes increasingly associated with both Syk and integrin beta3 upon platelet activation. Analysis of HIP-55 deficient platelets revealed reduced fibrinogen binding upon thrombin stimulation, suggesting HIP-55 to be an important regulator of platelet function.
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PMID:Proteomic analysis of resting and thrombin-stimulated platelets reveals the translocation and functional relevance of HIP-55 in platelets. 1972 75

Patterns of authority beliefs were examined among peer crowds in 598 middle school (M=12.97 years), early high school (M=15.10 years), and late high school adolescents (M=18.25 years). Participants reported beliefs regarding the boundaries of personal authority across personal, prudential, conventional, moral, and multifaceted issues. As expected, analyses revealed persistent differences in belief patterns among crowds within each age group. Tough and Alternative crowds asserted personal authority across all issues, while Prep and Outcast crowds endorsed parental authority. Jock, Hip Hop, and Normal crowds presented with shared-control patterns, but each crowd ceded and asserted authority over different issues. Discussion focused on crowds' roles in the development of group differences in the boundaries of personal authority.
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PMID:Adolescent peer crowds and patterns of belief in the boundaries of personal authority. 1993 43

Oral jewelry is popular. One of the most widely spread types are so-called tooth diamonds made of composite materials which are applied to the teeth with an adhesive. Note that parents are required to sign a release form for under-aged patients in Switzerland. Tooth cap grills and gold teeth are considered status symbols within the Hip-Hop fashion scene. However, tooth ornaments favour the accumulation of plaque and can diminish the ability to articulate. With respect to jewelry in oral soft tissue especially tongue and lip piercings are of significance to dentists. Besides the systemic complications, which are mostly caused by a lack of hygiene or the failure of noting medical contraindications by the piercer, local complications occur frequently. After surgery, pain, swelling, infections as well as hemorrhages or hematomas can be observed. Long-term effects can be problematic: gingival recession can be discernes mainly in the case of lip piercings the loss of hard tooth substance in the case of tongue piercings. Because of that, conservation therapies can become indespensable. Patients wearing dental jewelry have to be aware of risks of tooth damage, and they regularly have to undergo dental check-ups. Information campaigns--for dentists as well as patients--are necessary.
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PMID:[Oral jewelry: a review]. 2011 40


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