title: Charaterization of bumarsin, a 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitor from Mesobuthus martensii Karsch venom.
abstract: Scorpion venoms are rich sources of bioactive peptides and are widely known for their ion channel inhibiting properties. We have isolated, cloned and characterized a venom protein (Bumarsin) from the Chinese scorpion, Mesobuthus martensii Karsch. Bumarsin cDNA encodes a 8132 Da, 72 amino acid mature protein that most probably exists in its native form as a Cys-bridged homodimer. We have identified this novel protein to be an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity. 0.6 μM of Bumarsin inhibits 32% of the HMG-CoA reductase activity, in comparison to 10 μM simvastatin which only inhibits 35% of the activity. RT-PCR and SELDI-TOF mass spectrometric studies demonstrate that bumarsin regulates the expression of both genes and proteins involved in cholesterol homeostasis. Our results suggest that bumarsin may provide a model for the design of novel drugs that can be used to modulate cholesterol homeostasis.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
authors.forename: S C
authors.initials: SC
authors.lastname: Chai
authors.forename: A
authors.initials: A
authors.lastname: Armugam
authors.forename: P N
authors.initials: PN
authors.lastname: Strong
authors.forename: K
authors.initials: K
authors.lastname: Jeyaseelan
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D060829:Arthropod Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001053:Apolipoproteins; D060829:Arthropod Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010455:Peptides; D010750:Phosphoproteins; D011994:Recombinant Proteins; D012604:Scorpion Venoms; C575770:bumarsin, Mesobuthus martensii; D000098682:Steroidogenic Acute Regulatory Protein; D017856:Phosphotransferases (Phosphate Group Acceptor); C022371:phosphomevalonate kinase