@article {50,
	title = {Molecular models of the interface between anterior pharynx-defective protein 1 (APH-1) and presenilin involving GxxxG motifs.},
	journal = {ChemMedChem},
	volume = {3},
	year = {2008},
	month = {2008 Apr},
	pages = {627-34},
	abstract = {Gamma-secretase is an integral membrane protease, which is a complex of four membrane proteins. Improper functioning of gamma-secretase was found to be critical in the pathogenesis of Alzheimer{\textquoteright}s disease. Despite numerous efforts, the structure of the protease as well as its proteolytic mechanism remains poorly understood. In this work we constructed a model of interactions between two proteins forming gamma-secretase: APH-1 and presenilin. This interface is based on a highly conserved GxxxGxxxG motif in the APH-1 protein. It can form a tight contact with a small-residue AxxxAxxxG motif in presenilin. Here, four binding modes based on similar structures involving GxxxG motifs in glycophorin and aquaporin were proposed and verified. The resulting best model employs antiparallel orientations of interacting helices and is in agreement with the currently accepted topology of both proteins. This model can be used for further structural characterization of gamma-secretase and its components.},
	keywords = {Alzheimer Disease, Amyloid Precursor Protein Secretases, Genotype, Humans, Membrane Proteins, Models, Molecular, Peptide Hydrolases, Presenilin-1},
	issn = {1860-7187},
	doi = {10.1002/cmdc.200700189},
	author = {Jozwiak, Krzysztof and Krzy{\'s}ko, Krystiana A and Bojarski, Lukasz and Gacia, Magdalena and Filipek, S{\l}awomir}
}
@article {52,
	title = {Two novel presenilin 1 gene mutations connected with frontotemporal dementia-like clinical phenotype: genetic and bioinformatic assessment.},
	journal = {Experimental neurology},
	volume = {200},
	year = {2006},
	month = {2006 Jul},
	pages = {82-8},
	abstract = {Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes are associated with early-onset familial Alzheimer{\textquoteright}s disease (EOAD). There are several reports describing mutations in PSEN1 in cases with frontotemporal dementia (FTD). We identified two novel mutations in the PSEN1 gene: L226F and L424H. The first mutation was detected in a patient with a clinical diagnosis of FTD and a post-mortem diagnosis of AD. The second mutation is connected with a clinical phenotype of variant AD with strong FTD signs. In silico modeling revealed that the mutations, as well as mutations used for comparison (F177L and L424R), change the local structure, stability and/or properties of the transmembrane regions of the presenilin 1 protein (PS1). In contrast, a silent non-synonymous substitution F175S is eclipsed by external residues and has no influence on PS1 interfacial surface. We suggest that in silico analysis of PS1 substitutions can be used to characterize novel PSEN1 mutations, to discriminate between silent polymorphisms and a potential disease-causing mutation. We also propose that PSEN1 mutations should be considered in FTD patients with no MAPT mutations.},
	keywords = {Adult, Computational Biology, Dementia, Diagnosis, Differential, Female, Genetic Testing, Humans, Male, Membrane Proteins, Models, Molecular, Mutation, Phenotype, Presenilin-1},
	issn = {0014-4886},
	doi = {10.1016/j.expneurol.2006.01.022},
	author = {Zekanowski, Cezary and Golan, Maciej P and Krzy{\'s}ko, Krystiana A and Lipczy{\'n}ska-{\L}ojkowska, Wanda and Filipek, S{\l}awomir and Kowalska, Anna and Rossa, Grzegorz and Pep{\l}o{\'n}ska, Beata and Styczy{\'n}ska, Maria and Maruszak, Aleksandra and Religa, Dorota and Wender, Mieczys{\l}aw and Kulczycki, Jerzy and Barcikowska, Maria and Ku{\'z}nicki, Jacek}
}
