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Many Mutations (many + mutation)

Distribution by Scientific Domains

Chemistry	50%

Selected Abstracts

Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa

EXPERIMENTAL DERMATOLOGY, Issue 7 2008
Ningning Dang
Abstract:, Dystrophic epidermolysis bullosa (DEB) is inherited in both an autosomal dominant DEB and autosomal recessive manner RDEB, both of which result from mutations in the type VII collagen gene (COL7A1). To date, 324 pathogenic mutations have been detected within COL7A1 in different variants of DEB; many mutations are clustered in exon 73 (10.74%) which is close to the 39 amino acid interruption region. Dominant dystrophic epidermolysis bullosa usually involves glycine substitutions within the triple helix of COL7A1 although other missense mutations, deletions or splice-site mutations may underlie some cases. In recessive dystrophic epidermolysis bullosa, the mutations include nonsense, splice site, deletions or insertions, ,silent' glycine substitutions within the triple helix and non-glycine missense mutations within the triple helix or non-collagenous NC-2 domain. The nature of mutations in COL7A1 and their positions correlate reasonably logically with the severity of the resulting phenotypes. [source]

Effective program against mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso

JOURNAL OF MEDICAL VIROLOGY, Issue 7 2007
J. Simpore
Abstract The present research was aimed to prevent mother-to-child transmission of HIV; to use RT-PCR in order to detect, 6 months after birth, infected children; and to test the antiretroviral resistance of both children and mothers in order to offer them a suitable therapy. At the Saint Camille Medical Centre, 3,127 pregnant women (aged 15,44 years) accepted to be enrolled in the mother-to-child transmission prevention protocol that envisages: (i) Voluntary Counselling and Testing for all the pregnant women; (ii) Antiretroviral therapy for HIV positive pregnant women and for their newborns; (iii) either powdered milk feeding or short breast-feeding and RT-PCR test for their children; (iv) finally, pol gene sequencing and antiretroviral resistance identifications among HIV positive mothers and children. Among the patients, 227/3,127 HIV seropositive women were found: 221/227 HIV-1, 4/227 HIV-2, and 2/227 mixed HIV infections. The RT-PCR test allowed the detection of 3/213 (1.4%) HIV infected children: 0/109 (0%) from mothers under ARV therapy and 3/104 (2.8%) from mothers treated with Nevirapine. All children had recombinant HIV-1 strain (CRF06_CPX) with: minor PR mutations (M36I, K20I) and RT mutations (R211K). Among them, two twins had Non-Nucleoside Reverse Transcriptase Inhibitor mutation (Y18CY). Both mothers acquired a major PR mutation (V8IV), investigated 6 months after a single-dose of Nevirapine. Prevention by single-dose of Nevirapine reduced significantly mother-to-child transmission of HIV, but caused many mutations and resistance to antiretroviral drugs. Based on present study the antiretroviral therapy protocol, together with the artificial-feeding, might represent the ideal strategy to avoid transmission of HIV from mother-to-child. J. Med. Virol. 79:873,879, 2007. © 2007 Wiley-Liss, Inc. [source]

Probing mechanisms of resistance to the tuberculosis drug isoniazid: Conformational changes caused by inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis

PROTEIN SCIENCE, Issue 8 2007
Nicole A. Kruh
Abstract The frontline tuberculosis drug isoniazid (INH) inhibits InhA, the NADH-dependent fatty acid biosynthesis (FAS-II) enoyl reductase from Mycobacterium tuberculosis (MTB), via formation of a covalent adduct with NAD+ (the INH-NAD adduct). Resistance to INH can be correlated with many mutations in MTB, some of which are localized in the InhA cofactor binding site. While the InhA mutations cause a substantial decrease in the affinity of InhA for NADH, surprisingly the same mutations result in only a small impact on binding of the INH-NAD adduct. Based on the knowledge that InhA interacts in vivo with other components of the FAS-II pathway, we have initiated experiments to determine whether enzyme inhibition results in structural changes that could affect protein,protein interactions involving InhA and how these ligand-induced conformational changes are modulated in the InhA mutants. Significantly, while NADH binding to wild-type InhA is hyperbolic, the InhA mutants bind the cofactor with positive cooperativity, suggesting that the mutations permit access to a second conformational state of the protein. While cross-linking studies indicate that enzyme inhibition causes dissociation of the InhA tetramer into dimers, analytical ultracentrifugation and size exclusion chromatography reveal that ligand binding causes a conformational change in the protein that prevents cross-linking across one of the dimer,dimer interfaces in the InhA tetramer. Interestingly, a similar ligand-induced conformational change is also observed for the InhA mutants, indicating that the mutations modulate communication between the subunits without affecting the two conformational states of the protein that are present. [source]

The ribbon of hydrogen bonds in globular proteins.

BIOPOLYMERS, Issue 2 2004

Abstract A study of the role of the hydrogen-bonding side chains in the ribbon of hydrogen bonds in globular proteins, using the papain family as an example, suggests that these side chains may be divided into three categories depending on their position in the molecule. In the first category, they form part of the local ribbon, in the second they form part of the ribbon at a site remote along the main chain, and in the third they play no role in the formation of the ribbon. The second case is particularly interesting because it provides a natural mechanism for the formation of the tertiary structure of the globular proteins. The results suggest that the robustness of the globular proteins towards mutations arises from the fact that many mutations that involve hydrogen-bonding side chains either leave the hydrogen bonding of the ribbon essentially unchanged or their hydrogen bonding plays no part in the formation of the ribbon in the first place. The results show that it is possible to obtain the ribbon of hydrogen bonds for a family of proteins whose data set's are of intermediate quality by studying the ribbons of several members of such a family and then taking an average over the different partial ribbons to create a standard ribbon of hydrogen bonds for the family as a whole. This method is used here to derive the standard ribbon for the papain family with papain itself, actinidin, and human liver cathepsin B as the representatives of the family. All three members of the family fit the standard ribbon with an accuracy of 85,91%. This result opens up the use of this technique for the study of a large number of globular proteins whose recorded data sets are of intermediate quality. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 178,191, 2004 [source]