Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Best's vitelliform macular dystrophy is an autosomal dominant disorder of unknown causes. To identify the underlying gene defect the disease locus has been mapped to an approximately 1.4-Mb region on chromosome 11q12-q13.1. As a prerequisite for its positional cloning we have assembled a high coverage PAC contig of the candidate region. Here, we report the construction of a primary transcript map that places a total of 19 genes within the Best's disease region. This includes 14 transcripts of as yet unknown function obtained by EST mapping and/or cDNA selection and five genes mapped previously to the interval (CD5, PGA, DDB1, FEN1, and FTH1). Northern blot analyses were performed to determine the expression profiles in various human tissues. At least three genes appear to be good candidates for Best's disease based on their abundant expression in retina or retinal pigment epithelium. Additional information on the functional properties of these genes, as well as mutation analyses in Best's disease patients, have to await their further characterization. [The GenBank/EMBL accession numbers and details of the isolation, localization, and characterization of ESTs and selected cDNAs are available as online supplements in Online Tables 1-3 at http://www.genome.org.]
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PMID:A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1. 944 87

In many GL-7ACA acylases, the first Ser residue at the N-terminal of beta-subunit is the catalytic center. In order to investigate relationship between the N-terminal structure and catalytic activities, peptide replacement and site-directed mutagenesis were performed at the N-terminal of beta-subunit of GL-7ACA acylase C130. When the N-terminal 8 amino acid residues of C130 were replaced by the corresponding sequence of penicillin acylases PAC and PGA, respectively, the first mutant B8PAC lost the activity of the acylase, and the second mutant B8PGA had lower activity with the K(m) value increasing from 0.44x10(-3)mol.L(-1) to 0.55x10(-3) mol.L(-1), and the k(cat) decreasing from 4.92 s(-1) to 1.64 s(-1). Although the substitution of Trp (beta4) by Tyr did not change the K(m) value, the k (cat) decreased to 2.29 s(-1). When the Trp was substitued by Leu, both the K ( m ) and k ( cat ) values decreased. Compared with the wild type, mutations of Ser (beta3) to Met, Ala and Cys caused decrease of K(m) values by 52.27%, 43.18% and 38.64%, respectively. Mutation of Asn (beta2) to Gln caused the K ( m ) value being increased by 5-fold, and k ( cat ) decreased by 10-fold. These results suggested that the N-terminal amino acid residues of beta-subunit in GL-7ACA acylase C130 are important for enzyme function.
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PMID:Mutagenesis of N-terminal Amino Acid Residues in beta-subunit of Glutaryl-7-amino-cephalosporanic Acid Acylase C130. 1203 60