(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Eukaryota: NE > Opisthokonta: NE > Metazoa: NE > Eumetazoa: NE > Bilateria: NE > Deuterostomia: NE > Chordata: NE > Craniata: NE > Vertebrata: NE > Gnathostomata: NE > Teleostomi: NE > Euteleostomi: NE > Sarcopterygii: NE > Dipnotetrapodomorpha: NE > Tetrapoda: NE > Amniota: NE > Mammalia: NE > Theria: NE > Eutheria: NE > Boreoeutheria: NE > Euarchontoglires: NE > Glires: NE > Rodentia: NE > Myomorpha: NE > Muroidea: NE > Muridae: NE > Murinae: NE > Rattus: NE > Rattus norvegicus: NE
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MDLRTMTQSLVALAEDNMAFFSSQGPGETARRLSNVFAGVREQALGLEPT LGQLLGVAHHFDLDTETPANGYRSLVHTARCCLAHLLHKSRYVASNRRSI FFRASHNLAELEAYLAALTQLRALAYYAQRLLTINRPGVLFFEGDEGLSA DFLQDYVTLHKGCFYGRCLGFQFTPAIRPFLQTLSIGLVSFGEHYKRNET GLSVTASSLFTGGRFAIDPELRGAEFERIIQNLDVHFWKAFWNITEIEVL SSLANMASTTVRVSRLLSLPPEAFEMPLTSDPKLTVTISPPLAHTGPGPV LARLISYDLREGQDSKMLNSLAKSEGPRLELRPRPQQAPRSRALVVHIHG GGFVAQTSKSHEPYLKNWAQELGVPIISIDYSLAPEAPFPRALEECFFAY CWAVKHCELLGSTGERICLAGDSAGGNLCITVSLRAAAYGVRVPDGIMAA YPVTTLQSSASPSRLLSLMDPLLPLSVLSKCVSAYSGTETEDHFDSDQKA LGVMGLVQRDTSLFLRDLRLGASSWLNSFLELSGRKPHKTPVACNRDTAP HGFWALTESMRRSVSEAALAQPEGLLGTDSLKKLTIKDLSFKGNSEPSDS PEMSQSMETLGPSTPSDVNFFLRSGNSQEEAETRDDISPMDGIPRVRAAF PDGFHPRRSSQGVLHMPLYSSPIVKNPFMSPLLAPDVMLKTLPPVHLVAC ALDPMLDDSVMFARRLKDLGQPVTLKVVEDLPHGFLSLAALCRETGRPRS CACSASG
Cyclipostins are bicyclic lipophilic phosphate natural products. We report here that synthesized individual diastereomers of cyclipostins P and R have nanomolar IC50s toward hormone sensitive lipase (HSL). The less potent diastereomers of these compounds have 10-fold weaker IC50s. The monocyclic phosphate analog of cyclipostin P is nearly as potent as the bicyclic natural product. Bicyclic phosphonate analogs of both cyclipostins exhibit IC50s similar to those of the weaker diastereomer phosphates (about 400nM). The monocyclic phosphonate analog of cyclipostin P has similar potency. A series of monocyclic phosphonate analogs in which a hydrophobic tail extends from the lactone side of the ring are considerably poorer inhibitors, with IC50s around 50muM. Finally cyclophostin, a related natural product inhibitor of acetylcholinesterase (AChE) that lacks the hydrocarbon tail of cyclipostins, is not active against HSL. These results indicate a critical SAR for these compounds, the hydrophobic tail. The smaller lactone ring is not critical to activity, a similarity shared with cyclophostin and AChE. The HSL kinetics of inhibition for the cyclipostin P trans diastereomer were examined in detail. The reaction is irreversible with a KI of 40nM and a rate constant for inactivation of 0.2min(-1). These results are similar to those observed for cyclophostin and AChE.
By catalyzing the rate-limiting step in adipose tissue lipolysis, hormone-sensitive lipase (HSL) is an important regulator of energy homeostasis. The role and importance of HSL in tissues other than adipose are poorly understood. We report here the cloning and expression of a testicular isoform, designated HSLtes. Due to an addition of amino acids at the NH2-termini, rat and human HSLtes consist of 1068 and 1076 amino acids, respectively, compared to the 768 and 775 amino acids, respectively, of the adipocyte isoform (HSLadi). A novel exon of 1.2 kb, encoding the human testis-specific amino acids, was isolated and mapped to the HSL gene, 16 kb upstream of the exons encoding HSLadi. The transcribed mRNA of 3.9 kb was specifically expressed in testis. No significant similarity with other known proteins was found for the testis-specific sequence. The amino acid composition differs from the HSLadi sequence, with a notable hydrophilic character and a high content of prolines and glutamines. COS cells, transfected by the 3.9-kb human testis cDNA, expressed a protein of the expected molecular mass (M(r) approximately 120,000) that exhibited catalytic activity similar to that of HSLadi. Immunocytochemistry localized HSL to elongating spermatids and spermatozoa; HSL was not detected in interstitial cells.
Rattus norvegicus (Rat) Dipeptidyl peptidase 9 DPP9