Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conserved sequence features in Saccharomyces cerevisiae CEN DNA are confined to a region of approximately 120 bp. The highly conserved 8 bp at the left (PuTCACPuTG) constitute the left boundary of a functional CEN DNA as shown by the analysis of a series of Bal31 deletions. The right boundary of a functional CEN DNA lies within the conserved 25 bp at the right (TGT-T-TG--TTCCGAA-----AAA) or a few base pairs further outside of the 120-bp region. One mutant which just lacks the left conserved DNA element PuTCACPuTG can still assemble into a partially functional mitotic centromere and it assembles into a well functioning meiotic centromere. The sequences between the two conserved terminal DNA elements can be increased in length (+50%) or in GC content (from 6% to 12%) without measurable changes in mitotic and meiotic segregations of plasmids carrying such CEN mutations. The naturally occurring length and GC content of this centromere DNA sequence element is, therefore, not essential for centromere function. We discuss the possibility that it partly acts as a hinge region between two domains. Finally, we tested integrations of CEN DNA into the genome and found a toleration of wild-type CEN6 DNA when present 3' of the LYS2 gene.
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PMID:Role of conserved sequence elements in yeast centromere DNA. 299 49

Endoleak after endoluminal abdominal aortic aneurysm repair is a relatively common occurrence. Depending on the type of endoleak involved, treatment strategies range from continued serial observation to urgent re-intervention. Type II, or branch vessel endoleaks, are often benign in terms of their natural history but can potentially be associated with progressive abdominal aortic aneurysm sac expansion, endograft migration, or even aneurysm rupture. Type V endoleaks, also known as endotension, may represent an undiagnosed type I-IV endoleak or a progressive accumulation of transudate through the interstices of the endograft. Treatment strategies therefore hinge on correctly identifying the etiology of the endotension. We discuss the diagnosis and management of type II and V endoleaks, with a focus on a device-specific approach to endoleak treatment.
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PMID:An algorithm for diagnosis and treatment of type II endoleaks and endotension after endovascular aneurysm repair. 1611 Mar 85

Nisin A is the most extensively studied lantibiotic and has been used as a preservative by the food industry since 1953. This 34 amino acid peptide contains three dehydrated amino acids and five thioether rings. These rings, resulting from one lanthionine and four methyllanthionine bridges, confer the peptide with its unique structure. Nisin A has two mechanisms of action, with the N-terminal domain of the peptide inhibiting cell wall synthesis through lipid II binding and the C-terminal domain responsible for pore-formation. The focus of this study is the three amino acid 'hinge' region (N 20, M 21 and K 22) which separates these two domains and allows for conformational flexibility. As all lantibiotics are gene encoded, novel variants can be generated through manipulation of the corresponding gene. A number of derivatives in which the hinge region was altered have previously been shown to possess enhanced antimicrobial activity. Here we take this approach further by employing simultaneous, indiscriminate site-saturation mutagenesis of all three hinge residues to create a novel bank of nisin derivative producers. Screening of this bank revealed that producers of peptides with hinge regions consisting of AAK, NAI and SLS displayed enhanced bioactivity against a variety of targets. These and other results suggested a preference for small, chiral amino acids within the hinge region, leading to the design and creation of producers of peptides with hinges consisting of AAA and SAA. These producers, and the corresponding peptides, exhibited enhanced bioactivity against Lactococcus lactis HP, Streptococcus agalactiae ATCC 13813, Mycobacterium smegmatis MC2155 and Staphylococcus aureus RF122 and thus represent the first example of nisin derivatives that possess enhanced activity as a consequence of rational design.
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PMID:Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives. 2424 24

Cytoplasmic dynein is a dimeric AAA(+) motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo-electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA(+) rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein's directionality and unusual stepping behaviour.
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PMID:Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules. 2636 35

Myotilin is a component of the sarcomere where it plays an important role in organisation and maintenance of Z-disk integrity. This involves direct binding to F-actin and filamin C, a function mediated by its Ig domain pair. While the structures of these two individual domains are known, information about their relative orientation and flexibility remains limited. We set on to characterise the Ig domain pair of myotilin with emphasis on its molecular structure, dynamics and phylogeny. First, sequence conservation analysis of myotilin shed light on the molecular basis of myotilinopathies and revealed several motifs in Ig domains found also in I-band proteins. In particular, a highly conserved Glu344 mapping to Ig domain linker, was identified as a critical component of the inter-domain hinge mechanism. Next, SAXS and molecular dynamics revealed that Ig domain pair exists as a multi-conformation species with dynamic exchange between extended and compact orientations. Mutation of AKE motif to AAA further confirmed its impact on inter-domain flexibility. We hypothesise that the conformational plasticity of the Ig domain pair in its unbound form is part of the binding partner recognition mechanism.
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PMID:Conformational plasticity and evolutionary analysis of the myotilin tandem Ig domains. 2863 18

Mitofusins are dynamin-related GTPases that drive mitochondrial fusion by sequential events of oligomerization and GTP hydrolysis, followed by their ubiquitylation. Here, we show that fusion requires a trilateral salt bridge at a hinge point of the yeast mitofusin Fzo1, alternatingly forming before and after GTP hydrolysis. Mutations causative of Charcot-Marie-Tooth disease massively map to this hinge point site, underlining the disease relevance of the trilateral salt bridge. A triple charge swap rescues the activity of Fzo1, emphasizing the close coordination of the hinge residues with GTP hydrolysis. Subsequently, ubiquitylation of Fzo1 allows the AAA-ATPase ubiquitin-chaperone Cdc48 to resolve Fzo1 clusters, releasing the dynamin for the next fusion round. Furthermore, cross-complementation within the oligomer unexpectedly revealed ubiquitylated but fusion-incompetent Fzo1 intermediates. However, Cdc48 did not affect the ubiquitylated but fusion-incompetent variants, indicating that Fzo1 ubiquitylation is only controlled after membrane merging. Together, we present an integrated model on how mitochondrial outer membranes fuse, a critical process for their respiratory function but also putatively relevant for therapeutic interventions.
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PMID:Plasticity in salt bridge allows fusion-competent ubiquitylation of mitofusins and Cdc48 recognition. 3174 May 65