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Proc Natl Acad Sci U S A. Oct 1, 1992; 89(19): 9257–9261.

Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains.


The three-dimensional structure of BirA, the repressor of the Escherichia coli biotin biosynthetic operon, has been determined by x-ray crystallography and refined to a crystallographic residual of 19.0% at 2.3-A resolution. BirA is a sequence-specific DNA-binding protein that also catalyzes the formation of biotinyl-5'-adenylate from biotin and ATP and transfers the biotin moiety to other proteins. The level of biotin biosynthetic enzymes in the cell is controlled by the amount of biotinyl-5'-adenylate, which is the BirA corepressor. The structure provides an example of a transcription factor that is also an enzyme. The structure of BirA is highly asymmetric and consists of three domains. The N-terminal domain is mostly alpha-helical, contains a helix-turn-helix DNA-binding motif, and is loosely connected to the remainder of the molecule. The central domain consists of a seven-stranded mixed beta-sheet with alpha-helices covering one face. The other side of the sheet is largely solvent-exposed and contains the active site. The C-terminal domain comprises a six-stranded, antiparallel beta-sheet sandwich. The location of biotin binding is consistent with mutations that affect enzymatic activity. A nearby loop has a sequence that has been associated with phosphate binding in other proteins. It is inferred that ATP binds in this region, adjacent to the biotin. It is proposed that the binding of corepressor to monomeric BirA may promote DNA binding by facilitating the formation of a multimeric BirA-corepressor-DNA complex. The structural details of this complex remain an open question, however.

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Selected References

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  • Eisenberg MA. Regulation of the biotin operon in E. coli. Ann N Y Acad Sci. 1985;447:335–349. [PubMed]
  • Cronan JE., Jr The E. coli bio operon: transcriptional repression by an essential protein modification enzyme. Cell. 1989 Aug 11;58(3):427–429. [PubMed]
  • Barker DF, Campbell AM. The birA gene of Escherichia coli encodes a biotin holoenzyme synthetase. J Mol Biol. 1981 Mar 15;146(4):451–467. [PubMed]
  • Eisenberg MA, Prakash O, Hsiung SC. Purification and properties of the biotin repressor. A bifunctional protein. J Biol Chem. 1982 Dec 25;257(24):15167–15173. [PubMed]
  • Howard PK, Shaw J, Otsuka AJ. Nucleotide sequence of the birA gene encoding the biotin operon repressor and biotin holoenzyme synthetase functions of Escherichia coli. Gene. 1985;35(3):321–331. [PubMed]
  • Prakash O, Eisenberg MA. Biotinyl 5'-adenylate: corepressor role in the regulation of the biotin genes of Escherichia coli K-12. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5592–5595. [PMC free article] [PubMed]
  • Cronan JE., Jr Expression of the biotin biosynthetic operon of Escherichia coli is regulated by the rate of protein biotination. J Biol Chem. 1988 Jul 25;263(21):10332–10336. [PubMed]
  • Brennan RG, Vasu S, Matthews BW, Otsuka AJ. Crystallization of the bifunctional biotin operon repressor. J Biol Chem. 1989 Jan 5;264(1):5–5. [PubMed]
  • Buoncristiani MR, Howard PK, Otsuka AJ. DNA-binding and enzymatic domains of the bifunctional biotin operon repressor (BirA) of Escherichia coli. Gene. 1986;44(2-3):255–261. [PubMed]
  • Anderson WF, Ohlendorf DH, Takeda Y, Matthews BW. Structure of the cro repressor from bacteriophage lambda and its interaction with DNA. Nature. 1981 Apr 30;290(5809):754–758. [PubMed]
  • McKay DB, Steitz TA. Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA. Nature. 1981 Apr 30;290(5809):744–749. [PubMed]
  • Steitz TA, Ohlendorf DH, McKay DB, Anderson WF, Matthews BW. Structural similarity in the DNA-binding domains of catabolite gene activator and cro repressor proteins. Proc Natl Acad Sci U S A. 1982 May;79(10):3097–3100. [PMC free article] [PubMed]
  • Brennan RG, Matthews BW. The helix-turn-helix DNA binding motif. J Biol Chem. 1989 Feb 5;264(4):1903–1906. [PubMed]
  • Subbarao N, Haneef I. Defining topological equivalences in macromolecules. Protein Eng. 1991 Dec;4(8):877–884. [PubMed]
  • Wierenga RK, Hol WG. Predicted nucleotide-binding properties of p21 protein and its cancer-associated variant. Nature. 1983 Apr 28;302(5911):842–844. [PubMed]
  • Weber PC, Ohlendorf DH, Wendoloski JJ, Salemme FR. Structural origins of high-affinity biotin binding to streptavidin. Science. 1989 Jan 6;243(4887):85–88. [PubMed]
  • Hendrickson WA, Pähler A, Smith JL, Satow Y, Merritt EA, Phizackerley RP. Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2190–2194. [PMC free article] [PubMed]
  • Jordan SR, Pabo CO. Structure of the lambda complex at 2.5 A resolution: details of the repressor-operator interactions. Science. 1988 Nov 11;242(4880):893–899. [PubMed]
  • Aggarwal AK, Rodgers DW, Drottar M, Ptashne M, Harrison SC. Recognition of a DNA operator by the repressor of phage 434: a view at high resolution. Science. 1988 Nov 11;242(4880):899–907. [PubMed]
  • Otwinowski Z, Schevitz RW, Zhang RG, Lawson CL, Joachimiak A, Marmorstein RQ, Luisi BF, Sigler PB. Crystal structure of trp repressor/operator complex at atomic resolution. Nature. 1988 Sep 22;335(6188):321–329. [PubMed]
  • Brennan RG, Roderick SL, Takeda Y, Matthews BW. Protein-DNA conformational changes in the crystal structure of a lambda Cro-operator complex. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8165–8169. [PMC free article] [PubMed]
  • Matthews BW. Protein-DNA interaction. No code for recognition. Nature. 1988 Sep 22;335(6188):294–295. [PubMed]
  • Otsuka A, Abelson J. The regulatory region of the biotin operon in Escherichia coli. Nature. 1978 Dec 14;276(5689):689–694. [PubMed]
  • Miller S, Lesk AM, Janin J, Chothia C. The accessible surface area and stability of oligomeric proteins. Nature. 328(6133):834–836. [PubMed]
  • Harrison SC. A structural taxonomy of DNA-binding domains. Nature. 1991 Oct 24;353(6346):715–719. [PubMed]
  • Kim B, Little JW. Dimerization of a specific DNA-binding protein on the DNA. Science. 1992 Jan 10;255(5041):203–206. [PubMed]

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