title: Molecular insights into the binding of coenzyme F420 to the conserved protein Rv1155 from Mycobacterium tuberculosis.
abstract: Coenzyme F420 is a deazaflavin hydride carrier with a lower reduction potential than most flavins. In Mycobacterium tuberculosis (Mtb), F420 plays an important role in activating PA-824, an antituberculosis drug currently used in clinical trials. Although F420 is important to Mtb redox metabolism, little is known about the enzymes that bind F420 and the reactions that they catalyze. We have identified a novel F420 -binding protein, Rv1155, which is annotated in the Mtb genome sequence as a putative flavin mononucleotide (FMN)-binding protein. Using biophysical techniques, we have demonstrated that instead of binding FMN or other flavins, Rv1155 binds coenzyme F420 . The crystal structure of the complex of Rv1155 and F420 reveals one F420 molecule bound to each monomer of the Rv1155 dimer. Structural, biophysical, and bioinformatic analyses of the Rv1155-F420 complex provide clues about its role in the bacterium.
authors: Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, 20892; Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom.
authors: Ellene H
authors: EH
authors: Mashalidis
authors: Apostolos G
authors: AG
authors: Gittis
authors: Aurelie
authors: A
authors: Tomczak
authors: Chris
authors: C
authors: Abell
authors: Clifton E
authors: CE
authors: Barry
authors: David N
authors: DN
authors: Garboczi
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D005420:Flavoproteins / Q000737:chemistry*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000472:pathogenicity; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation; D012256:Riboflavin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D005420:Flavoproteins; C015084:coenzyme F420; D012256:Riboflavin
keywords: Mycobacterium tuberculosis; Rv1155; coenzyme F420; conserved hypothetical protein
references: Nature. 2011 Jan 27;469(7331):483-90
references: 21270886
references: FEBS Lett. 2005 Jan 3;579(1):215-21
references: 15620716
references: Nat Methods. 2011;8(10):785-6
references: 21959131
references: PLoS One. 2011;6(11):e27643
references: 22110704
references: Structure. 2012 Jan 11;20(1):101-12
references: 22244759
references: Lancet. 2012 May 19;379(9829):1902-13
references: 22608339
references: Nucleic Acids Res. 2013 Jan;41(Database issue):D808-15
references: 23203871
references: Nat Protoc. 2013 Nov;8(11):2309-24
references: 24157549
references: Nature. 2000 Jun 22;405(6789):962-6
references: 10879539
references: J Mol Biol. 2001 Jan 19;305(3):567-80
references: 11152613
references: J Agric Food Chem. 2001 Mar;49(3):1123-7
references: 11312822
references: J Mol Biol. 2001 Jul 20;310(4):817-26
references: 11453690
references: Arch Microbiol. 2001 Jul;176(1-2):37-43
references: 11479701
references: EMBO J. 2001 Dec 3;20(23):6561-9
references: 11726492
references: J Bacteriol. 2002 May;184(9):2420-8
references: 11948155
references: Appl Environ Microbiol. 2002 Nov;68(11):5750-5
references: 12406775
references: Nucleic Acids Res. 2003 Jan 1;31(1):258-61
references: 12519996
references: Protein Sci. 2003 Jul;12(7):1455-63
references: 12824491
references: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41
references: 14681378
references: J Am Chem Soc. 2004 Feb 4;126(4):1047-54
references: 14746472
references: Protein Sci. 2005 Jul;14(7):1840-9
references: 15937276
references: Acta Crystallogr D Biol Crystallogr. 2005 Nov;61(Pt 11):1492-9
references: 16239726
references: Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):431-6
references: 16387854
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W116-8
references: 16844972
references: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Aug 1;62(Pt 8):735-42
references: 16880544
references: BMC Bioinformatics. 2006;7:255
references: 16704727
references: Protein Expr Purif. 2007 Jul;54(1):38-44
references: 17376702
references: Nat Protoc. 2007;2(11):2728-33
references: 18007608
references: J Biol Chem. 2008 Jun 20;283(25):17531-41
references: 18434308
references: J Bacteriol. 1972 Oct;112(1):527-31
references: 5079072
references: Antimicrob Agents Chemother. 2009 Sep;53(9):3720-5
references: 19528280
references: Biochemistry. 2009 Oct 27;48(42):10098-105
references: 19761261
references: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
references: 20124702
references: BMC Microbiol. 2010;10:132
references: 20429878
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
references: 20457744
references: J Bacteriol. 2010 Nov;192(21):5788-98
references: 20675471
references: Mol Microbiol. 2010 Nov;78(3):561-75
references: 20807200
references: PLoS One. 2010;5(12):e15803
references: 21209917
references: Structure. 2004 Mar;12(3):361-70
references: 15016352
references: J Comput Chem. 2004 Oct;25(13):1605-12
references: 15264254
references: Biochem Biophys Res Commun. 1964 Apr 22;15(5):414-9
references: 4378502
references: Biochemistry. 1984 Oct 9;23(21):4868-72
references: 6541948
references: J Bacteriol. 1996 May;178(10):2861-6
references: 8631674
references: Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4285-8
references: 10200254
references: Biochim Biophys Acta. 1960 Jun 3;40:532-4
references: 13812439
references: Curr Pharm Des. 2004;10(26):3239-62
references: 15544513
references: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2115-25
references: 15572764
references: Nat Rev Microbiol. 2005 Jan;3(1):70-80
references: 15608701
references: Tuberculosis (Edinb). 2011 Jan;91(1):1-7
references: 20980199