Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease
Reexamination Certificate
2008-04-18
2009-06-09
Kosar, Andrew D (Department: 1656)
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Transferase other than ribonuclease
C435S041000, C435S007400
Reexamination Certificate
active
07544498
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.
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Kuzuyama Tomohisa
Noel Joseph P.
Richard Stephane P.
Foley & Lardner LLP
Gebreyesus Kagnew H
Kosar Andrew D
Reiter Stephen E.
The Salk Institute for Biological Studies
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