Type I polyketide synthase PikAIV
Details
- Name
- Type I polyketide synthase PikAIV
- Kind
- protein
- Synonyms
- Not Available
- Gene Name
- pikAIV
- UniProtKB Entry
- Q9ZGI2TrEMBL
- Organism
- Streptomyces venezuelae
- NCBI Taxonomy ID
- 54571
- Amino acid sequence
>lcl|BSEQ0012824|Type I polyketide synthase PikAIV MTSSNEQLVDALRASLKENEELRKESRRRADRRQEPMAIVGMSCRFAGGIRSPEDLWDAV AAGKDLVSEVPEERGWDIDSLYDPVPGRKGTTYVRNAAFLDDAAGFDAAFFGISPREALA MDPQQRQLLEASWEVFERAGIDPASVRGTDVGVYVGCGYQDYAPDIRVAPEGTGGYVVTG NSSAVASGRIAYSLGLEGPAVTVDTACSSSLVALHLALKGLRNGDCSTALVGGVAVLATP GAFIEFSSQQAMAADGRTKGFASAADGLAWGEGVAVLLLERLSDARRKGHRVLAVVRGSA INQDGASNGLTAPHGPSQQHLIRQALADARLTSSDVDVVEGHGTGTRLGDPIEAQALLAT YGQGRAPGQPLRLGTLKSNIGHTQAASGVAGVIKMVQALRHGVLPKTLHVDEPTDQVDWS AGSVELLTEAVDWPERPGRLRRAGVSAFGVGGTNAHVVLEEAPAVEESPAVEPPAGGGVV PWPVSAKTSAALDAQIGQLAAYAEDRTDVDPAVAARALVDSRTAMEHRAVAVGDSREALR DALRMPEGLVRGTVTDPGRVAFVFPGQGTQWAGMGAELLDSSPEFAAAMAECETALSPYV DWSLEAVVRQAPSAPTLDRVDVVQPVTFAVMVSLAKVWQHHGITPEAVIGHSQGEIAAAY VAGALTLDDAARVVTLRSKSIAAHLAGKGGMISLALSEEATRQRIENLHGLSIAAVNGPT ATVVSGDPTQIQELAQACEADGIRARIIPVDYASHSAHVETIENELADVLAGLSPQTPQV PFFSTLEGTWITEPALDGGYWYRNLRHRVGFAPAVETLATDEGFTHFIEVSAHPVLTMTL PDKVTGLATLRREDGGQHRLTTSLAEAWANGLALDWASLLPATGALSPAVPDLPTYAFQH RSYWISPAGPGEAPAHTASGREAVAETGLAWGPGAEDLDEEGRRSAVLAMVMRQAASVLR CDSPEEVPVDRPLREIGFDSLTAVDFRNRVNRLTGLQLPPTVVFQHPTPVALAERISDEL AERNWAVAEPSDHEQAEEEKAAAPAGARSGADTGAGAGMFRALFRQAVEDDRYGEFLDVL AEASAFRPQFASPEACSERLDPVLLAGGPTDRAEGRAVLVGCTGTAANGGPHEFLRLSTS FQEERDFLAVPLPGYGTGTGTGTALLPADLDTALDAQARAILRAAGDAPVVLLGHSGGAL LAHELAFRLERAHGAPPAGIVLVDPYPPGHQEPIEVWSRQLGEGLFAGELEPMSDARLLA MGRYARFLAGPRPGRSSAPVLLVRASEPLGDWQEERGDWRAHWDLPHTVADVPGDHFTMM RDHAPAVAEAVLSWLDAIEGIEGAGK
- Number of residues
- 1346
- Molecular Weight
- 141912.755
- Theoretical pI
- 4.68
- GO Classification
- Functionshydrolase activity, acting on ester bonds / phosphopantetheine binding / transferase activityProcessesbiosynthetic process
- General Function
- Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide. The thioesterase can use a series of diketide-N-acetylcysteamine (SNAC) thioesters, but has a strong preference for the 2-methyl-3-ketopentanoyl-SNAC over the stereoisomers of 2-methyl-3-hydroxyacyl-SNAC (PubMed:12379101, PubMed:12733905).
- Specific Function
- 3-oxoacyl-[acyl-carrier-protein] synthase activity
- Pfam Domain Function
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasmic
- Gene sequence
>lcl|BSEQ0007752|969 bp ATGGCATTTTCCCCGCAGGGCGGCCGACACGAGCTCGGTCAGAACTTCCTCGTCGACCGG TCAGTGATCGACGAGATCGACGGCCTGGTGGCCAGGACCAAGGGTCCGATACTGGAGATC GGTCCGGGTGACGGCGCCCTGACCCTGCCGCTGAGCAGGCACGGCAGGCCGATCACCGCC GTCGAGCTCGACGGCCGGCGCGCGCAGCGCCTCGGTGCCCGCACCCCCGGTCATGTGACC GTGGTGCACCACGACTTCCTGCAGTACCCGCTGCCGCGCAACCCGCATGTGGTCGTCGGC AACGTCCCCTTCCATCTGACGACGGCGATCATGCGGCGGCTGCTCGACGCCCAGCACTGG CACACCGCCGTCCTCCTCGTCCAGTGGGAGGTCGCCCGGCGCCGGGCCGGCGTCGGCGGG TCGACGCTGCTGACGGCCGGCTGGGCGCCCTGGTACGAGTTCGACCTGCACTCCCGGGTC CCCGCGCGGGCCTTCCGTCCGATGCCGGGCGTGGACGGAGGAGTACTGGCCATCCGGCGG CGGTCCGCGCCGCTCGTGGGCCAGGTGAAGACGTACCAGGACTTCGTACGCCAGGTGTTC ACCGGCAAGGGGAACGGGCTGAAGGAGATCCTGCGGCGGACCGGGCGGATCTCGCAGCGG GACCTGGCGACCTGGCTGCGGAGGAACGAGATCTCGCCGCACGCGCTGCCCAAGGACCTG AAGCCCGGGCAGTGGGCGTCGCTGTGGGAGCTGACCGGCGGCACGGCCGACGGATCCTTC GACGGTACGGCGGGCGGTGGCGCGGCCGGATCGCACGGGGCGGCTCGGGTCGGGGCCGGT CACCCGGGCGGCCGGGTGTCCGCGAGCCGGCGGGGCGTGCCGCAGGCGCGGCGCGGCCGG GGGCATGCGGTACGGAGCTCCACGGGGACCGAGCCGAGGTGGGGCAGGGGGCGGGCGGAG AGCGCGTGA
- Chromosome Location
- Not Available
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID Q9ZGI2 UniProtKB Entry Name Q9ZGI2_STRVZ GenBank Protein ID 3800832 GenBank Gene ID AF079138 PDB ID(s) 1MN6, 1MNA, 1MNQ, 2H7X, 2H7Y, 2HFJ, 2HFK, 3F5H - General References
- Xue Y, Zhao L, Liu HW, Sherman DH: A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: architecture of metabolic diversity. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12111-6. [Article]
- Tsai SC, Lu H, Cane DE, Khosla C, Stroud RM: Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthases. Biochemistry. 2002 Oct 22;41(42):12598-606. [Article]
- Giraldes JW, Akey DL, Kittendorf JD, Sherman DH, Smith JL, Fecik RA: Structural and mechanistic insights into polyketide macrolactonization from polyketide-based affinity labels. Nat Chem Biol. 2006 Oct;2(10):531-6. Epub 2006 Sep 10. [Article]
- Akey DL, Kittendorf JD, Giraldes JW, Fecik RA, Sherman DH, Smith JL: Structural basis for macrolactonization by the pikromycin thioesterase. Nat Chem Biol. 2006 Oct;2(10):537-42. Epub 2006 Sep 10. [Article]
- Buchholz TJ, Geders TW, Bartley FE 3rd, Reynolds KA, Smith JL, Sherman DH: Structural basis for binding specificity between subclasses of modular polyketide synthase docking domains. ACS Chem Biol. 2009 Jan 16;4(1):41-52. doi: 10.1021/cb8002607. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details (3R,4S,5S,7R,9E,11R,12R)-12-ETHYL-4-HYDROXY-3,5,7,11-TETRAMETHYLOXACYCLODODEC-9-ENE-2,8-DIONE experimental unknown target Details [(3R,4S)-4-HYDROXY-3-METHYL-2-OXOHEXYL]PHOSPHONIC ACID experimental unknown target Details [(3R,4S,5S,7R)-4,8-DIHYDROXY-3,5,7-TRIMETHYL-2-OXOOCTYL]PHOSPHONIC ACID experimental unknown target Details