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)

An algorithm for encoding long strings of building blocks, like 4 DNA bases (adenine-A, cytosine-C, thymine-T, and guanidine-G), 20 natural amino acids (from Alanine Ala to Valine-Val, plus the stop triplet), or all 64 possible base triplets (from AAA to TTT), into "zigzag" or "spectrum-like" representations is suggested. The new encoding scheme can be derived in the 3-, 2-, or 1-dimensional form depending on the user's wishes. The only information, besides the string for which the "spectrum-like" representation is sought, is the initial positioning of the complete set of units from which the string is composed, i.e., four positions for A, C, G, and T, or 20 positions for natural amino acids plus stop, etc. This initial positioning can be initialized in either the 3-, 2-, or 1-D form. As an illustration of the suggested encoding scheme of the visual and chemometric comparison of the first 10 exon strings of the beta globin gene of 10 different species, each string consisting of about 100 basic amino acids long is shown.
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PMID:Algorithm for coding DNA sequences into "spectrum-like" and "zigzag" representations. 1580 92

Class III adenylyl cyclases usually possess six highly conserved catalytic residues. Deviations in these canonical amino acids are observed in several putative adenylyl cyclase genes as apparent in several bacterial genomes. This suggests that a variety of catalytic mechanisms may actually exist. The gene Rv0386 from Mycobacterium tuberculosis codes for an adenylyl cyclase catalytic domain fused to an AAA-ATPase and a helix-turn-helix DNA-binding domain. In Rv0386, the standard substrate, adenine-defining lysine-aspartate couple is replaced by glutamine-asparagine. The recombinant adenylyl cyclase domain was active with a V(max) of 8 nmol cAMP.mg(-1).min(-1). Unusual for adenylyl cyclases, Rv0386 displayed 20% guanylyl cyclase side-activity with GTP as a substrate. Mutation of the glutamine-asparagine pair either to alanine residues or to the canonical lysine-aspartate consensus abolished activity. This argues for a novel mechanism of substrate selection which depends on two non-canonical residues. Data from individual and coordinated point mutations suggest a model for purine definition based on an amide switch related to that previously identified in cyclic nucleotide phosphodiesterases.
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PMID:Adenylyl cyclase Rv0386 from Mycobacterium tuberculosis H37Rv uses a novel mode for substrate selection. 1595 67

In humans, eight types of histone H1 exist (H1.1-H1.5, H1 degrees , H1t and H1oo), all consisting of a highly conserved globular domain and less conserved N- and C-terminal tails. Although the precise functions of these isoforms are not yet understood, and H1 subtypes have been found to be dispensable for mammalian development, it is now clear that specific functions may be assigned to certain individual H1 subtypes. Moreover, microsequence variations within the isoforms, such as polymorphisms or mutations, may have biological significance because of the high degree of sequence conservation of these proteins. This study used a hydrophilic interaction liquid chromatographic method to detect sequence variants within the subtypes. Two deviations from wild-type H1 sequences were found. In K562 erythroleukemic cells, alanine at position 17 in H1.2 was replaced by valine, and, in Raji B lymphoblastoid cells, lysine at position 173 in H1.4 was replaced by arginine. We confirmed these findings by DNA sequencing of the corresponding gene segments. In K562 cells, a homozygous GCC-->GTC shift was found at codon 18, giving rise to H1.2 Ala17Val because the initial methionine is removed in H1 histones. Raji cells showed a heterozygous AAA-->AGA codon change at position 174 in H1.4, corresponding to the Lys173Arg substitution. The allele frequency of these sequence variants in a normal Swedish population was found to be 6.8% for the H1.2 GCC-->GTC shift, indicating that this is a relatively frequent polymorphism. The AAA-->AGA codon change in H1.4 was detected only in Raji cells and was not present in a normal population or in six other cell lines derived from individuals suffering from Burkitt's lymphoma. The significance of these sequence variants is unclear, but increasing evidence indicates that minor sequence variations in linker histones may change their binding characteristics, influence chromatin remodeling, and specifically affect important cellular functions.
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PMID:Characterization of sequence variations in human histone H1.2 and H1.4 subtypes. 1600 66

Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection.
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PMID:A surface groove essential for viral Bcl-2 function during chronic infection in vivo. 1620 Oct 11

The FtsH proteases, also called AAA proteases, are membrane-bound ATP-dependent metalloproteases. The Arabidopsis genome contains a total of 12 FtsH-like genes. Two of them, AtFtsH4 and AtFtsH11, encode proteins with a high similarity to Yme1p, a subunit of the i-AAA complex in yeast mitochondria. Phylogenetic analysis groups the AtFtsH4, AtFtsH11 and Yme1 proteins together, with AtFtsH4 being the most similar to Yme1. Using immunological method we demonstrate here that AtFtsH4 is an exclusively mitochondrial protein while AtFtsH11 is found in both chloroplasts and mitochondria. AtFtsH4 and AtFtsH11 proteases are integral parts of the inner mitochondrial membrane and expose their catalytic sites towards the intermembrane space, same as yeast i-AAA. Database searches revealed that orthologs of AtFtsH4 and AtFtsH11 are present in both monocotyledonous and dicotyledonous plants. The two plant i-AAA proteases differ significantly in their termini: the FtsH4 proteins have a characteristic alanine stretch at the C-terminal end while FtsH11s have long N-terminal extensions. Blue-native gel electrophoresis revealed that AtFtsH4 and AtFtsH11 form at least two complexes with apparent molecular masses of about 1500 kDa. This finding implies that plants, in contrast to fungi and metazoa, have more than one complex with a topology similar to that of yeast i-AAA.
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PMID:Plant mitochondria contain at least two i-AAA-like complexes. 1624 55

Ankyrins contain significant amino acid identity and are co-expressed in many cell types yet maintain unique functions in vivo. Recent studies have identified the highly divergent C-terminal domain in ankyrin-B as the key domain for driving ankyrin-B-specific functions in cardiomyocytes. Here we identify an intramolecular interaction between the C-terminal domain and the membrane-binding domain of ankyrin-B using pure proteins in solution and the yeast two-hybrid assay. Through extensive deletion and alanine-scanning mutagenesis we have mapped key residues for interaction in both domains. Amino acids (1597)EED(1599) located in the ankyrin-B C-terminal domain and amino acids Arg(37)/Arg(40) located in ANK repeat 1 are necessary for inter-domain interactions in yeast two-hybrid assays. Furthermore, conversion of amino acids EED(1597) to AAA(1597) leads to a loss of function in the localization of inositol 1,4,5-trisphosphate receptors in ankyrin-B mutant cardiomyocytes. Physical properties of the ankyrin-B C-terminal domain determined by circular dichroism spectroscopy and hydrodynamic parameters reveal it is unstructured and highly extended in solution. Similar structural studies performed on full-length 220-kDa ankyrin-B harboring alanine substitutions, (1597)AAA(1599), reveal a more extended conformation compared with wild-type ankyrin-B. Taken together these results suggest a model of an extended and unstructured C-terminal domain folding back to bind and potentially regulate the membrane-binding domain of ankyrin-B.
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PMID:Isoform specificity of ankyrin-B: a site in the divergent C-terminal domain is required for intramolecular association. 1636 89

We measured the temperature-dependent electronic circular dichroism (ECD) spectra of AX, XA, and XG dipeptides in D2O. The spectra of all XA and AX peptides indicate a substantial population of the polyproline II (PPII) conformation, while the ECD spectra of LG, KG, PG, and AG were found to be quantitatively different from the alanine-based dipeptides. Additional UV absorption data indicate that the ECD spectra of the XG peptides stem from electronic coupling between the peptide and the C-terminal group, and that spectral differences reflect different orientations of the latter. We also measured the 1H NMR spectra of the investigated dipeptides to determine the 3JHalphaNH coupling constants for the C-terminal residue. The observed temperature dependence of the ECD spectra and the respective room-temperature 3JHalphaNH coupling constants were analyzed by a two-state model encompassing PPII and a beta-like conformation. The PPII propensity of alanine in the XA series is only slightly modulated by the N-terminal side chain, and is larger than 50%. As compared to AA, XA peptides containing L, P, S, K V, E, T, and I all cause a relative stabilization of the extended beta-strand conformation. The PPII fractions of XA peptides varied between 0.64 for AA and 0.58 for DA, whereas the PPII fractions of AX peptides were much lower. From the investigated AX peptides, only AL and AQ showed the expected PPII propensity. We found that AT, AI, and AV clearly prefer an extended beta-strand conformation. A quantitative comparison of AA, AAA, and AAAA revealed a hierarchy AAAA > AAA approximately AA for the PPII population, in agreement with predictions from MD calculations and results from Raman optical activity studies (McColl et al. J. Am. Chem. Soc. 2004, 126, 5076).
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PMID:Conformational analysis of XA and AX dipeptides in water by electronic circular dichroism and 1H NMR spectroscopy. 1657 Oct 11

Rubisco activase is a member of the AAA(+) family in which arginines located in the Box VII and Sensor 2 domains are a recurrent feature and typically contribute to ATP-binding/hydrolysis or an inter-subunit interface. Replacement of R241 or R244 in Box VII or R294 or R296 in Sensor 2 with alanine in tobacco activase did not greatly alter the binding of ATP or ADP. However, ATP hydrolysis was minimal (R241A and R244A) or greatly diminished (R296A) and none of these mutants were able to activate Rubisco. R241, R244 and R296 were also required for nucleotide-dependent conformational changes detected by intrinsic fluorescence and limited proteolysis. ATP-induced oligomerization, monitored by gel filtration, was not observed with the wild type and mutant tobacco activases in contrast to spinach activase and a R239A mutant (corresponding to R244A in tobacco). Thus, there is not a strict correlation of oligomerization with ATP hydrolysis and intrinsic fluorescence.
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PMID:Identification of critical arginine residues in the functioning of Rubisco activase. 1671 73

The trans-translation system in bacteria promotes recycling of stalled ribosomes and targets incomplete peptides for proteolysis. In Escherichia coli, loss of trans-translation function has little effect on growth under normal laboratory conditions. Among the subtle phenotypes of tmRNA-deficient mutants is the inability to plate certain lambda imm(P22) phages. This phenotype is dependent on the ribosome recycling functions of the trans-translation system but is independent of its proteolysis-targeting activity. The experiments described here show that translation of the first (resume) codon of the tmRNA open reading frame by a tRNA is both necessary and sufficient for ribosome recycling. While a variety of sense codons can replace the naturally-occurring GCA alanine codon as the resume codon, both AAA and AAG lysine codons are non-functional resume codons. These results suggest that the main function of tmRNA in releasing stalled ribosomes is to supply a stop codon and so facilitate termination and subsequent ribosome recycling.
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PMID:Minimal translation of the tmRNA tag-coding region is required for ribosome release. 1741 10

Dysregulation of the proteasome has been documented in a variety of human diseases such as Alzheimer, muscle atrophy, cataracts etc. Proteolytic activity of 26 S proteasome is ATP- and ubiquitin-dependent. O-GlcNAcylation of Rpt2, one of the AAA ATPases in the 19 S regulatory cap, shuts off the proteasome through the inhibition of ATPase activity. Thus, through control of the flux of glucose into O-GlcNAc, the function of the proteasome is coupled to glucose metabolism. In the present study we found another metabolic control of the proteasome via cAMP-dependent protein kinase (PKA). Contrary to O-Glc-NAcylation, PKA activated proteasomes both in vitro and in vivo in association with the phosphorylation at Ser(120) of another AAA ATPase subunit, Rpt6. Mutation of Ser(120) to Ala blocked proteasome function. The stimulatory effect of PKA and the phosphorylation of Rpt6 were reversible by protein phosphatase 1 gamma. Thus, hormones using the PKA system can also regulate proteasomes often in concert with glucose metabolism. This finding might lead to novel strategies for the treatment of proteasome-related diseases.
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PMID:Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. 1756 87


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