title: Structural analysis of a putative aminoglycoside N-acetyltransferase from Bacillus anthracis.
abstract: For the last decade, worldwide efforts for the treatment of anthrax infection have focused on developing effective vaccines. Patients that are already infected are still treated traditionally using different types of standard antimicrobial agents. The most popular are antibiotics such as tetracyclines and fluoroquinolones. While aminoglycosides appear to be less effective antimicrobial agents than other antibiotics, synthetic aminoglycosides have been shown to act as potent inhibitors of anthrax lethal factor and may have potential application as antitoxins. Here, we present a structural analysis of the BA2930 protein, a putative aminoglycoside acetyltransferase, which may be a component of the bacterium's aminoglycoside resistance mechanism. The determined structures revealed details of a fold characteristic only for one other protein structure in the Protein Data Bank, namely, YokD from Bacillus subtilis. Both BA2930 and YokD are members of the Antibiotic_NAT superfamily (PF02522). Sequential and structural analyses showed that residues conserved throughout the Antibiotic_NAT superfamily are responsible for the binding of the cofactor acetyl coenzyme A. The interaction of BA2930 with cofactors was characterized by both crystallographic and binding studies.
authors: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
authors: Maria M
authors: MM
authors: Klimecka
authors: Maksymilian
authors: M
authors: Chruszcz
authors: Jose
authors: J
authors: Font
authors: Tatiana
authors: T
authors: Skarina
authors: Igor
authors: I
authors: Shumilin
authors: Olena
authors: O
authors: Onopryienko
authors: Przemyslaw J
authors: PJ
authors: Porebski
authors: Marcin
authors: M
authors: Cymborowski
authors: Matthew D
authors: MD
authors: Zimmerman
authors: Jeremy
authors: J
authors: Hasseman
authors: Ian J
authors: IJ
authors: Glomski
authors: Lukasz
authors: L
authors: Lebioda
authors: Alexei
authors: A
authors: Savchenko
authors: Aled
authors: A
authors: Edwards
authors: Wladek
authors: W
authors: Minor
references: Trends Microbiol. 1997 Jun;5(6):234-40
references: 9211644
references: Acta Crystallogr D Biol Crystallogr. 1993 Jan 1;49(Pt 1):148-57
references: 15299555
references: Drug Resist Updat. 2001 Apr;4(2):106-17
references: 11512519
references: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6665-70
references: 15870211
references: Biochemistry. 2001 Mar 27;40(12):3700-9
references: 11297438
references: Appl Microbiol Biotechnol. 2006 Mar;70(2):140-50
references: 16391922
references: Methods Mol Med. 2008;142:261-71
references: 18437320
references: J Mol Biol. 2007 Sep 21;372(3):774-97
references: 17681537
references: Arch Biochem Biophys. 2005 Jan 1;433(1):212-26
references: 15581578
references: Protein Expr Purif. 2002 Jun;25(1):8-15
references: 12071693
references: Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61
references: 10089316
references: Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22
references: 18156677
references: Nat Struct Biol. 1999 May;6(5):458-63
references: 10331874
references: Proteins. 2000 Oct 1;41(1):47-57
references: 10944393
references: Am J Med. 1986 Jun 30;80(6B):126-37
references: 3088998
references: Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
references: 15299374
references: Sci Am. 1998 Mar;278(3):46-53
references: 9487702
references: Clin Microbiol Rev. 2003 Jul;16(3):430-50
references: 12857776
references: Clin Infect Dis. 2001 Sep 15;33 Suppl 3:S108-15
references: 11524705
references: J Synchrotron Radiat. 2004 Jan 1;11(Pt 1):49-52
references: 14646132
references: Clin Infect Dis. 1997 Jan;24 Suppl 1:S46-62
references: 8994779
references: Structure. 2001 Nov;9(11):1095-106
references: 11709173
references: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references: 15299926
references: Protein Sci. 2003 Mar;12(3):426-37
references: 12592013
references: J Biol Chem. 1978 Sep 10;253(17):5902-7
references: 681327
references: Proteins. 2003 Feb 15;50(3):437-50
references: 12557186
references: Methods Enzymol. 1997;276:307-26
references: 27754618
references: J Med Chem. 2004 Mar 25;47(7):1739-49
references: 15027865
references: J Synchrotron Radiat. 2006 Jan;13(Pt 1):30-45
references: 16371706
references: Bioinformatics. 2005 Jun 15;21(12):2832-8
references: 15802286
references: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1937-40
references: 12393925
references: Protein Eng. 2001 Dec;14(12):993-1000
references: 11809930
references: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
references: 11517324
references: Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1833-9
references: 15388930
references: Arch Biochem Biophys. 1967 Mar;119(1):41-9
references: 6052434
references: Bioinformatics. 2006 Mar 1;22(5):621-2
references: 16407320
references: Acta Crystallogr D Biol Crystallogr. 2006 Aug;62(Pt 8):859-66
references: 16855301
references: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references: 15572765
references: Chem Biol. 2002 Apr;9(4):455-63
references: 11983334
references: Bioinformatics. 2003 Feb 12;19(3):427-8
references: 12584134