Solution structure and function of YndB, an AHSA1 protein from Bacillus subtilis.
The solution structure of the Bacillus subtilis protein YndB has been solved using NMR to investigate proposed biological functions. The YndB structure exhibits the helix-grip fold, which consists of a β-sheet with two small and one long α-helix, forming a hydrophobic cavity that preferentially binds lipid-like molecules. Sequence and structure comparisons with proteins from eukaryotes, prokaryotes, and archaea suggest that YndB is very similar to the eukaryote protein Aha1, which binds to the middle domain of Hsp90 and induces ATPase activity. On the basis of these similarities, YndB has been classified as a member of the activator of Hsp90 ATPase homolog 1-like protein (AHSA1) family with a function that appears to be related to stress response. An in silico screen of a compound library of ∼ 18,500 lipids was used to identify classes of lipids that preferentially bind YndB. The in silico screen identified, in order of affinity, the chalcone/hydroxychalcone, flavanone, and flavone/flavonol classes of lipids, which was further verified by 2D (1) H-(15) N HSQC NMR titration experiments with trans-chalcone, flavanone, flavone, and flavonol. All of these compounds are typically found in plants as precursors to various flavonoid antibiotics and signaling molecules. The sum of the data suggests an involvement of YndB with the stress response of B. subtilis to chalcone-like flavonoids released by plants due to a pathogen infection. The observed binding of chalcone-like molecules by YndB is likely related to the symbiotic relationship between B. subtilis and plants.
Stark
Jaime L
JL
Department of Chemistry, University of Nebraska Lincoln, Lincoln, Nebraska 68588-0304, USA.
Mercier
Kelly A
KA
Mueller
Geoffrey A
GA
Acton
Thomas B
TB
Xiao
Rong
R
Montelione
Gaetano T
GT
Powers
Robert
R
D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D019295:Computational Biology; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000032:analysis; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D017433:Protein Structure, Secondary; D012996:Solutions; D040681:Structural Homology, Protein; D013816:Thermodynamics; D017186:Titrimetry; D014584:User-Computer Interface
C515652:AHSA1 protein, human; D001426:Bacterial Proteins; D008024:Ligands; D008055:Lipids; D018832:Molecular Chaperones; D049294:Phospholipid Transfer Proteins; D012996:Solutions
J Biol Chem. 2003 May 9;278(19):17228-35
12604615
Plant Signal Behav. 2007 Sep;2(5):349-50
19704655
Curr Opin Microbiol. 2004 Dec;7(6):579-86
15556029
Curr Top Med Chem. 2003;3(1):39-53
12577990
Nucleic Acids Res. 2004 Feb 03;32(2):742-8
14762202
Curr Opin Chem Biol. 2006 Jun;10(3):194-202
16675286
Nat Struct Biol. 1996 Dec;3(12):1040-5
8946858
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5349-54
18388203
Biomol NMR Assign. 2009 Dec;3(2):191-4
19888688
Mol Cell. 2002 Dec;10(6):1307-18
12504007
Structure. 1996 Jun 15;4(6):705-14
8805554
Drug Discov Today. 2008 Feb;13(3-4):172-9
18275915
J Mol Graph Model. 2003 Mar;21(5):449-62
12543140
J Biomol NMR. 1999 Mar;13(3):289-302
10212987
Microbiol Res. 2009;164(5):493-513
18845426
J Struct Funct Genomics. 2009 Apr;10(2):101-6
19288278
Protein Sci. 2009 Mar;18(3):606-18
19241370
J Comput Chem. 2004 Oct;25(13):1605-12
15264254
J Am Chem Soc. 2006 Nov 29;128(47):15292-9
17117882
Plant Physiol. 2003 Jul;132(3):1153-61
12857798
Nat Biotechnol. 1999 Sep;17(9):859-63
10471925
Methods Enzymol. 2005;394:210-43
15808222
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83
17452350
Proteins. 2006 Oct 1;65(1):15-26
16862531
Curr Opin Chem Biol. 2004 Feb;8(1):76-80
15036160
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
9757107
ACS Chem Biol. 2006 Aug 22;1(7):451-60
17168523
J Comput Chem. 2007 Apr 30;28(6):1145-52
17274016
Methods Mol Biol. 2004;278:313-52
15318002
Biosci Biotechnol Biochem. 2003 Feb;67(2):225-43
12728980
Trends Biotechnol. 2003 Apr;21(4):146-7; discussion 147-8
12679059
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W606-12
17584797
Bioinformatics. 2008 Dec 1;24(23):2780-1
18818215
Nat Prod Rep. 2003 Feb;20(1):79-110
12636085
J Lipid Res. 2005 May;46(5):839-61
15722563
Proteins. 2004 Nov 1;57(2):225-42
15340911
Microbiol Mol Biol Rev. 2000 Mar;64(1):180-201
10704479
Curr Opin Biotechnol. 2001 Apr;12(2):155-60
11287230
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10487-92
16027363
J Bacteriol. 2003 Jan;185(2):466-74
12511492
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9197-9
7937740
J Biomol NMR. 1995 Nov;6(3):277-93
8520220
Planta. 2007 Jul;226(2):283-97
17554552
PLoS Comput Biol. 2008 Sep 26;4(9):e1000168
18818721
Nucleic Acids Res. 2007 Jan;35(Database issue):D291-7
17135200
BMC Bioinformatics. 2007 Jan 26;8:27
17257425
Proteins. 2005 Jun 1;59(4):662-72
15822098
Molecules. 2007 Jul 05;12(7):1290-306
17909485
Drug Discov Today. 2002 Sep 15;7(18 Suppl):S125-30
12546878
Proteins. 2006 Oct 1;65(1):124-35
16862592
Trends Biochem Sci. 1999 Apr;24(4):130-2
10322415
Nucleic Acids Res. 2008 Jan;36(Database issue):D281-8
18039703
Biochemistry. 2000 Dec 19;39(50):15399-409
11112525
Cell. 1989 Jan 27;56(2):203-14
2643474
J Comb Chem. 2008 Nov-Dec;10(6):948-58
18831571
Protein Sci. 2004 Feb;13(2):540-4
14718655
Curr Protoc Bioinformatics. 2002 Aug;Chapter 2:Unit 2.3
18792934
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W116-8
16844972
J Comput Aided Mol Des. 2003 Aug;17(8):525-36
14703123
OMICS. 2004 Winter;8(4):322-33
15703479
Plant Physiol. 2001 Jun;126(2):485-93
11402179
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2754-9
11880627
BMC Evol Biol. 2008 Oct 15;8:286
18922149
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
9254694
Nucleic Acids Res. 2008 Jan;36(Database issue):D419-25
18000004
Biopolymers. 2003 Jan;68(1):76-90
12579581
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6600-4
8692863
Annu Rev Phytopathol. 2006;44:135-62
16602946
Nat Biotechnol. 2005 May;23(5):591-9
15867911
Annu Rev Physiol. 2001;63:193-213
11181954
J Med Chem. 2002 May 23;45(11):2213-21
12014959
J Am Chem Soc. 2008 Jan 16;130(2):535-45
18088118
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13731-6
8943003
J Mol Biol. 1990 Oct 5;215(3):403-10
2231712
Drug Discov Today. 2006 Jul;11(13-14):580-94
16793526
J Lipid Res. 2009 Apr;50 Suppl:S9-14
19098281
J Mol Biol. 2002 May 24;319(1):209-27
12051947
Nat Genet. 1993 Mar;3(3):266-72
8485583
Proteins. 2007 Mar 1;66(4):778-95
17186527
Nat Struct Biol. 2002 Jul;9(7):507-11
12055623