Mycocyclosin synthase

Details

Name
Mycocyclosin synthase
Synonyms
  • 1.14.21.9
  • Cytochrome P450 121
  • Cytochrome P450 MT2
Gene Name
cyp121
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0051128|Mycocyclosin synthase
MTATVLLEVPFSARGDRIPDAVAELRTREPIRKVRTITGAEAWLVSSYALCTQVLEDRRF
SMKETAAAGAPRLNALTVPPEVVNNMGNIADAGLRKAVMKAITPKAPGLEQFLRDTANSL
LDNLITEGAPADLRNDFADPLATALHCKVLGIPQEDGPKLFRSLSIAFMSSADPIPAAKI
NWDRDIEYMAGILENPNITTGLMGELSRLRKDPAYSHVSDELFATIGVTFFGAGVISTGS
FLTTALISLIQRPQLRNLLHEKPELIPAGVEELLRINLSFADGLPRLATADIQVGDVLVR
KGELVLVLLEGANFDPEHFPNPGSIELDRPNPTSHLAFGRGQHFCPGSALGRRHAQIGIE
ALLKKMPGVDLAVPIDQLVWRTRFQRRIPERLPVLW
Number of residues
396
Molecular Weight
43255.455
Theoretical pI
Not Available
GO Classification
Functions
carbon monoxide binding / cyclase activity / heme binding / iron ion binding / monooxygenase activity / oxidoreductase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
Processes
growth / oxidation-reduction process / sterol metabolic process
Components
cytoplasm
General Function
Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate.
Specific Function
Carbon monoxide binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051129|Mycocyclosin synthase (cyp121)
ATGACCGCGACCGTTCTGCTCGAGGTCCCGTTCTCTGCACGTGGGGATCGGATTCCTGAC
GCCGTCGCAGAATTACGAACCCGCGAGCCTATCCGCAAGGTACGGACCATTACCGGCGCC
GAAGCCTGGCTCGTCTCCTCGTATGCACTGTGCACACAGGTGCTCGAGGATCGGCGTTTT
TCCATGAAGGAAACCGCCGCTGCCGGCGCCCCCCGCCTGAACGCGCTGACTGTTCCACCC
GAAGTGGTCAACAACATGGGAAACATCGCCGACGCGGGACTGCGCAAGGCGGTGATGAAA
GCGATCACACCCAAGGCACCCGGGTTGGAGCAATTCCTACGAGACACCGCGAACTCGCTG
CTGGACAACCTGATTACCGAGGGCGCACCAGCCGATCTGCGCAATGACTTCGCCGACCCG
CTGGCCACTGCCCTGCACTGCAAGGTTCTGGGCATCCCGCAAGAAGACGGCCCGAAGCTG
TTCCGTAGCTTGAGTATCGCTTTCATGAGTTCGGCCGACCCGATCCCCGCCGCGAAGATC
AACTGGGATCGCGACATCGAATACATGGCCGGAATTCTGGAAAACCCAAACATCACGACC
GGCCTCATGGGTGAGCTCAGCCGCCTCCGGAAAGATCCCGCCTACTCGCACGTCTCCGAC
GAACTATTCGCGACCATCGGCGTCACTTTCTTCGGTGCCGGCGTCATCTCAACCGGCAGC
TTCCTCACCACCGCGCTGATATCGCTGATACAACGCCCGCAACTTCGGAACTTGTTGCAC
GAGAAGCCGGAACTGATCCCGGCCGGTGTAGAGGAACTGCTGCGGATCAATCTCTCCTTC
GCCGACGGGTTACCGCGCCTGGCCACCGCCGACATCCAGGTCGGCGACGTGCTGGTCCGC
AAGGGGGAGCTGGTGCTGGTGCTGCTCGAGGGCGCCAACTTCGATCCCGAGCACTTCCCT
AACCCGGGCAGCATCGAACTCGACCGGCCCAACCCCACCTCGCACCTCGCGTTCGGCCGC
GGCCAACACTTCTGTCCTGGATCAGCTCTCGGTCGCCGCCACGCACAGATCGGCATCGAA
GCGCTGTTGAAAAAGATGCCCGGCGTCGACCTGGCTGTGCCCATCGACCAATTGGTCTGG
CGCACCCGATTCCAAAGACGCATCCCCGAACGCCTTCCGGTGCTCTGGTAG
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP9WPP7
UniProtKB Entry NameCP121_MYCTU
General References
  1. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [Article]
  2. McLean KJ, Cheesman MR, Rivers SL, Richmond A, Leys D, Chapman SK, Reid GA, Price NC, Kelly SM, Clarkson J, Smith WE, Munro AW: Expression, purification and spectroscopic characterization of the cytochrome P450 CYP121 from Mycobacterium tuberculosis. J Inorg Biochem. 2002 Sep 20;91(4):527-41. [Article]
  3. Mowat CG, Leys D, McLean KJ, Rivers SL, Richmond A, Munro AW, Ortiz Lombardia M, Alzari PM, Reid GA, Chapman SK, Walkinshaw MD: Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr. 2002 Apr;58(Pt 4):704-5. Epub 2002 Mar 22. [Article]
  4. Raman K, Yeturu K, Chandra N: targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis. BMC Syst Biol. 2008 Dec 19;2:109. doi: 10.1186/1752-0509-2-109. [Article]
  5. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [Article]
  6. Leys D, Mowat CG, McLean KJ, Richmond A, Chapman SK, Walkinshaw MD, Munro AW: Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450. J Biol Chem. 2003 Feb 14;278(7):5141-7. Epub 2002 Nov 14. [Article]
  7. Seward HE, Roujeinikova A, McLean KJ, Munro AW, Leys D: Crystal structure of the Mycobacterium tuberculosis P450 CYP121-fluconazole complex reveals new azole drug-P450 binding mode. J Biol Chem. 2006 Dec 22;281(51):39437-43. Epub 2006 Oct 6. [Article]
  8. McLean KJ, Carroll P, Lewis DG, Dunford AJ, Seward HE, Neeli R, Cheesman MR, Marsollier L, Douglas P, Smith WE, Rosenkrands I, Cole ST, Leys D, Parish T, Munro AW: Characterization of active site structure in CYP121. A cytochrome P450 essential for viability of Mycobacterium tuberculosis H37Rv. J Biol Chem. 2008 Nov 28;283(48):33406-16. doi: 10.1074/jbc.M802115200. Epub 2008 Sep 24. [Article]
  9. Belin P, Le Du MH, Fielding A, Lequin O, Jacquet M, Charbonnier JB, Lecoq A, Thai R, Courcon M, Masson C, Dugave C, Genet R, Pernodet JL, Gondry M: Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2009 May 5;106(18):7426-31. doi: 10.1073/pnas.0812191106. Epub 2009 Apr 22. [Article]
  10. Hudson SA, McLean KJ, Surade S, Yang YQ, Leys D, Ciulli A, Munro AW, Abell C: Application of fragment screening and merging to the discovery of inhibitors of the Mycobacterium tuberculosis cytochrome P450 CYP121. Angew Chem Int Ed Engl. 2012 Sep 10;51(37):9311-6. doi: 10.1002/anie.201202544. Epub 2012 Aug 13. [Article]
  11. Fonvielle M, Le Du MH, Lequin O, Lecoq A, Jacquet M, Thai R, Dubois S, Grach G, Gondry M, Belin P: Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121: insights from biochemical studies and crystal structures. J Biol Chem. 2013 Jun 14;288(24):17347-59. doi: 10.1074/jbc.M112.443853. Epub 2013 Apr 25. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB027214-IodopyrazoleexperimentalunknownDetails
DB08761(3S,6S)-3,6-bis(4-hydroxybenzyl)piperazine-2,5-dioneexperimentalunknownDetails