Aromatic prenyltransferases, nucleic acids encoding same and...

Details Aromatic prenyltransferases, nucleic acids encoding same and... Aromatic prenyltransferases, nucleic acids encoding same and...

2008-04-22

2008-04-22

Nashed, Nashaat T. (Department: 1656)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving transferase

C435S193000

Reexamination Certificate

active

11342328

ABSTRACT:
In accordance with the present invention, a novel aromatic prenyltransferase, Orf2 fromStreptomycessp. strain CL190, involved in naphterpin biosynthesis has been identified and the structure thereof elucidated. This prenyltransferase catalyzes the formation of a C—C bond between a prenyl group and a compound containing an aromatic nucleus, and also displays C—O bond formation activity. Numerous crystallographic structures of the prenyltransferase have been solved and refined, e.g., (1) prenyltransferase complexed with a buffer molecule (TAPS), (2) prenyltransferase as a binary complex with geranyl diphosphate (GPP) and Mg2+, and prenyltransferase as ternary complexes with a non-hydrolyzable substrate analogue, geranyl S-thiolodiphosphate (GSPP) and either (3) 1,6-dihydroxynaphthalene (1,6-DHN), or (4) flaviolin (i.e., 2,5,7-trihydroxy-1,4-naphthoquinone, which is the oxidized product of 1,3,6,8-tetrahydroxynaphthalene (THN)). These structures have been solved and refined to 1.5 Å, 2.25 Å, 1.95 Å and 2.02 Å, respectively. This first structure of an aromatic prenyltransferase displays an unexpected and non-canonical (β/α)-barrel architecture. The complexes with both aromatic substrates and prenyl containing substrates and analogs delineate the active site and are consistent with a proposed electrophilic mechanism of prenyl group transfer. These structures also provide a mechanistic basis for understanding prenyl chain length determination and aromatic co-substrate recognition in this structurally unique family of aromatic prenyltransferases. This structural information is useful for predicting the aromatic prenyltransferase activity of proteins.

REFERENCES:
Wiencek et al. New strategies for protein crystal growth. Ann. Rev. Biomed. Eng. 1999, 1, 505-534.
Ke et al. Crystallization of RNA and RNA-protein complexes. Methods 34, 2004, 408-414.
Gilliland et al. Crystallization of biological molecules for X-ray diffraction studies. Current Opinion in Structure Biology 1996, 6, 595-603.
Altschul et al., Gapped BLAST and PSI-BLAST: A New Generation of Protein Database Search Programs,J. Mol. Biol. 215:403-410 (1990).
Altschul et al., Basic Local Alignment Search Tool,Nucl. Acids Res. 25:3389-3402 (1977).
Austin and Noel, The Chalcone Synthase Superfamily of Type III Polyketide Synthases, Nat Prod Rep 20(1):79-110 (2003).
Funa et al., A New Pathway For Polyketide Synthesis in Microorganisms, Nature 400(6747):897-9 (1999).
Gerlt and Raushel, Evolution of function in (β/α)8-Barrel Enzymes, Curr Opin Chem Biol 7(2):252-64 (2003).
Henikoff & Henikoff, Amino Acid Substitution Matrices From Protein Blocks,Proc. Natl. Acad. Sci. USA89:10915 (1989).
Jez et al., Dissection of Malonyl-Coenzyme A Decarboxylation From Polyketide Formation in the Reaction Mechanism of a Plant Polyketide Synthase, Biochemistry 39(5):890-902 (2000).
Lattman, Use of the Rotation and Translation Functions,Meth. Enzymol. 115:55-77 (1985).
Liang, Structure, Mechanism and Function of Prenyltransferases, Eur J Biochem 269(14):3339-54 (2002).
Long et al., Reaction Path of Protein Farnesyltransferase at Atomic Resolution, Biochemistry 37(27):9612-8 (1998).
Long et al., Cocrystal Structure of Protein Farnesyltransferase Complexed with a Farnesyl Diphosphate Substrate, Nature 419(6907):645-50 (2002).
Milligan et al., Identification of a Potent Phytoestrogen in Hops (Humulus lupulusL.) and Beer, J Clin Endocrinol Metab 84:2249-52 (1999).
Needleman & Wunsch, A General Method Applicable to the Search for Similarities in the Amino Acid Sequence of Two Proteins,J. Mol. Biol. 48:443 (1970).
Park et al., Crystal Structure of Protein Farnesyltransferase at 2.25 Angstrom Resolution, Science 275(5307):1800-4 (1997).
Person & Lipman, Improved Tools for Biological Sequence Comparison,Proc. Natl. Acad. Sci. USA85:2444 (1988).
Pojer et al., CloQ, a Prenyltransferase Involved in Clorobiocin Biosynthesis, Proc Natl Acad Sci USA 100:2316-2321 (2003).
Sacchettini et al., Crystal Structure of Rat Intestinal Fatty-acid-binding Protein, J Mol Biol 208(2):327-39 (1989).
Shin-ya, et al., Isolation and Structural Elucidation of an Antioxidative Agent, Naphterpin, in J. Antibiot. (Tokyo) 43, 444-447 (1990).
Smith & Waterman, Comparison of Biosequences,Adv. Appl. Math. 2:482 (1981).
Takagi et al., A Gene Cluster for the Mevalonate Pathway from Streptomyces sp. Strain CL190, J Bacteriol 182:41534157 (2000).
Tarshis et al., Crystal Structure of Recombinant Farnesyl Diphosphate Synthase at 2.6-Å Resolution, Biochemistry 33(36):10871-7 (1994).
Xu et al., The Adipocyte Lipid-binding Protein at 1.6-Å Resolution, J Mol Biol 268(11):7874-84 (1993).

Affiliated with

Also associated with

Rating

Aromatic prenyltransferases, nucleic acids encoding same and... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Aromatic prenyltransferases, nucleic acids encoding same and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Aromatic prenyltransferases, nucleic acids encoding same and... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3923288