The following text describes a protein:
Function:
Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of the antitumor fumiquinazolines that confer a dual-usage capability to defend against phagocytes in the environment and animal hosts. The simplest member is fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from anthranilic acid (Ant), tryptophan (Trp), and alanine (Ala). The trimodular NRPS fmqA is responsible for FQF formation. Modules 1, 2 and 3 of fmqA are predicted to activate and load Ant, Trp and Ala, respectively, providing for the assembly of an Ant-Trp-Ala-S-enzyme intermediate that would undergo double cyclization for chain release and generation of the tricyclic 6-6-6 product fumiquinazoline F. The presence of an E domain predicted for module 2 of fmqA is consistent with epimerization of L-Trp to D-Trp during assembly to generate the R-stereocenter at C14 of FQF. The FAD-dependent monooxygenase fmqB and the monomodular NRPS fmqC then maturate FQF to FQA. FmqB oxidizes the 2',3'-double bond of the indole side chain of FQF, and fmqC activates L-Ala as the adenylate, installs it as the pantetheinyl thioester on its carrier protein domain, and acylates the oxidized indole for subsequent intramolecular cyclization to create the 6-5-5-imidazolindolone of FQA. The FAD-linked oxidoreductase fmqD introduces a third layer of scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by catalyzing the formation of a transient imine within the pyrazinone ring. FQC subsequently converts nonenzymatically to the known cyclic aminal FQD.
Subcellular Localization:
Cytoplasmic vesicle. Note=Does not localize to endocytic vesicles, vacuoles nor mitochondria.
Domain:
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase. NRPS12 has the following architecture: A-T-C-A-T-E-C-A-T-C.
Sequence:
MERLEAKNQTTKHGERMAPQRYSVLRDEKCLFPVRNDGKLLVDEWRVTELAISSGEKGLKLCRTTCPTAGADPRYLAAAAWALLLWRFAEVDTVQIGLQDIPPGANEDILEAGLKRGMKVLAASRRQVQLLNELWQGDTWSISDADPTCYSYFDTGIVICRGNSQDCLAKCRSPNQLRKANGEACNVLLVLELDLDSNWRKCFLAYKTTVLTDIQATHLKSSFEEVVELARAGRGIPLSEICLVSRRQLDQIGKWNERALVQPKFKAMHQVVHDRATDRRHHPAVIAADRALSYSELETLSLKVAYRLRGSGVQPGDLIPVCFCKSSWAIVAMLAINKLGAAFVPLDPSQPVNRLKSITRQLDATLAVTSPENQSLVEDLVTTTVVVSETTVSELVDVHNEIVLPACDPGAPAYCLFTSGSTGKPKGCVVDHAALASVATHSHALHLGPTSRVLQFASFTFGVSLIEVWCTLAAGGTVCLPSDSDRVSRLADAIRSMGVDWCILTPTVLATLEPEAVPNLRTILVAGEPLKKAQFSLWAERARLFQAYGFTEWAGICCVSPQIRSIGDVGIIGTPANARCWLVEPGNPNQLAPIGAVAELAVEGPSLAQGYLHDPEKTAATLIPPPRWRAQYGHADGKRIYTTGDLVYYDSNGMLRYVSRKDRQVKIRGQRIDLAEPEYHIAQACCTIRNVVLDAIVPADSNGDAILVAFVLPSRDESSSNGGHDSPLFAVPDDHFTSSVRQLTSFLEDKLPDYMVPRLFLQLKETPVTITGKIARQKLREAAEALRHDELVALAGLETRVLPPNTHKETLIHQLVVELLHLPPEMVGMNHNFFSLGGDSVSVMKLVSRAKRVGLSFTVKDVFRSPQLGDLARLTDVVNSGAAQHMPPFSLLDRGAQPGLLSMAAKICQVESSMIQDIYPCTPLQEGMMTLSAAKAGSYIARFVYRLEEHVDSPRFRRAWEMTVEATPILRTRIISASDGRLYQVVIQEKFRWDDDGQPSGECVQNGQDRHMLLGEPLTHAALVRDRNQDGSLSTVFVLTMHHSVCDRWSVGLIMDSVETAYTGQTLTTNSMGPFLQYIQQLQGGDAFWRSQFVGVKAEVFPSLPSPEYTPTPTETIDLSVELRDAVPGGHTIANAIRLAWALVISHYTSCSDVVFGVTISGRAVPVPDIERIIGPIIATVPLRVRLKESSTVLEALKAIQDQSMEMIPFEQLGLRQIRKLSPEAEEACNFQSQLVVQPAWGDENRSLFATCEAGAAAEGGFAAYALSMICQLVGSSQIDVRTEFDPKVIQAPIMQRIVHHFVYTLQYLLAHPDARVAEIPVVSPGEKQLLRQWNGIVPPASHQCVHEIIQQRQIERPTSTAVWAWDGQLTYAELGELSDRLAEYLATKGVQPEVIVPVCLEKSYWTTVAMLGISKAGGAFALLDPSQPEQRLQSICHQLNSAVILTSEKNRDLAGKLASHPIVLSLQSSRRWGHGPAKQAPATARPDHTLYVAFTSGSTGTPKGVVIEHRSFCTSALALNRITGVNSESRMLQFAGYSFDGSIMEMLSALMAGACVCVPSEFQRRNELVAAAAKFELTHAHLTPSVARHLLRGNPEFTKTLVSVGEPMTASDVADWASNGQCKVMNGYGPAECAVSTTIQAAVTSASDPKNIGFPVAGVCWVVHPENHDILLPPGAVGELLIEGPTLARGYLNEPDKTAAAFIPLPAWIKDIRPEQPHGRLYKSGDLVRYNADGSFQYIGRRDSQIKLRGQRIELDEVEKHVYQCWPGVIAVVAVEMVSFTPATQTLVAFVVVEEHVDTTGDILAAPTQEFTGQVAVAQARLREAIPAFMVPEIFIPLLVLPQSASGKTDRRRLRSIATACTREKLAAYGAVGTGTKREPTSVAEREMQAIWAQALNLPLAEIGMDDSFYQLGGDSITAMQVVAHARSKGLAVTMDSILRLKSISKIMSHESSLSPAIVHIDEEEDVWFALSPIQQMFFDRQPSGWDRFSQVFLLRVSQPVTASQLQMALHTLVSKHPMLRARFAKQHDGSWRQVITSKIQESYRCRSHRLNRRSSVDGVVSSGACSLSIQKGPLIAVDLMSREDGAQYLSIVIHHLVVDLVSWRIILADLEAMLRGENPMANHSTPFQTWCRLQAEYARQYLSPQHAFPTDLPDHYHQDPSVFWGLAGQPNLVRDSRRQVFTLDEHTTRQLLGAANAAFATRTDEVLHAVLLYSFLKVFPHRIAPLTFSEGHGREPWDSAIDLSQTVGWFTTMWPVVAELQQNHSFLEVVCRVKDARRAVPCNGWAYFVSRYLNPSGRQAFQQFHPVELVFNYAGEYQQFNQAGAFFIPDMPEYQGSLDAGEQIQRFGIFEVFASVVRGCLQFQFMYNRYMKHQLEIQKWIESCRQTLIEGCSTLIAAKPSRTLSDFPLLPLTYSTLRELLDVTLPTAGVSVENVEDIYPCSPSQRGMLIAQAKAAHNYNASVTWSIRSRIDSRPNVARLKAAWCEVVKRHAILRTVFVESPWPESYMDQVVLQNVSPEFVFCRGSDSLPQSISSPGQTRWSKGQCQHIMRVWERDNGDILCRLDLSHAIMDRTTLAIIQKDLSLAYDERLLPGRAPLYRDYISYIYQQDSESARQYWQGYLEGVEPCEFPTLNPVDPSITKEWGNLYRTLEDRRRLEEFCRTHSVTPWNVAGLAWAMVLRSFTRTDSVCFGYVKSGRDLPIDGIAGTAGPVFNPLPCRVHLTERLTVRETIGRLQEEYLQSLAHQSFPLSDIHRLAGVTSGVLFNTSVAVQTEVASEAEEAKRSLEFTTVAMEDGTEDDMVITLVPRGGELVLHLRHRSRTLTTDQASTVLATFEKALCSILANAEAPMTSIDVFSDHDKAILWSRNRRVPDAVESCVHELIQKHCVERPHSPAVNAWDGAFTYGQLDELSSRLAVYLAAQGVGPNVVVPLCFEKTRWTPIAMMGVMKAGGAFLLLDPSYPLQRLKDICADIDCRLVVSSTTHEAMSRELASTVVVVGEDRHHWQLENTSHTITMPKVRPADALYVVFTSGSTGKPKGVVIEHRSYCSGALDHIRSYNLTPQSRVLQFSSYAFDISIVEQLSVLIAGGCICVISESQRKNSLGEAATALQANHAMLIPSVARLVRHEDLSTITSLSLAGECMQETDVSYWAQHVRLMNGYGPAECSALSLVQPCVLPHSDPHDIGYPVGSVAWVVDPHDHHKLVPNGAVGELLIEGPIVGRGYINNAEKTAEVFIEPPTWLRTLRGHCTSRLYKTGDLVRANPSGSLSILGRKDRQVKLRGQRLELGEVEANVQHCFPGALDVVADLLPSSRGGKPQLVAMVFQNAERAARIAPESDSKLIAEPSVDFMQSATTAETRLRQTVPNFMVPSMFLPLAQIPRTHSDKVDRNSLLKAVAAMSSIELQAYKASVDAGHCSTRAPSTEEEKKLAEIWADVLKVPVEHIGADDNFLLSGGDSIDAMKAAAFCRAAGMALSVADIFAHPVLSDLAKVAVPKSLNGSSTSHQPFSLSPVDSPKDLHMSLMEQGLVPPGSALADLLPGTQAQQFFIERGTFHSYNFSIRGPLDRCRLQKTCTAILSRHSILRTKFLQYEGRLIQIVLDNLETPFTHYTTDGDLLEFCKSLWERDLAALDGLGRLPCKFTLVSRSEQEHVFTIQISHAQWDGVSIPRLFSDIAAIYNQIPLPSTTHFADYVYHRSSRDERPAFDFWKKYLRGSSMPVPFPATNCQDREHKTQWTFQGIKNPRLPAGITMASLVKAACGFHLCQLLSQNDVVFGHTVNGRNLALDNVEALLGCCLNFIPLRVMLQPSWTVLDLLAHVQEQYTRALPHEHLELRDIFRHSTPWPADTQLSFIVQHQNIELHHNIALDGLQVQYSKFAQFDPLTEVWIFSEPHPDRLEIQVCANTRVLSEDQARALCRRLCDLIEFFSASPDCPLSKVVDHMDRPGLLAEEKVLN