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Structure of Anthranilate Phosphoribosyltransferase from the enterobacterium Erwinia Carotovora

Choel Kim

Appointment Period: 1999-2002, Grant Years: [15,16,17]

Choel KimDuring my research, I solved the structure of anthranilate phosphoribosyltranferase from the enterobacterium Erwinia carotovora. The enzyme structure has a novel phosphoribosyltranferase fold, and displays close homology to the structure of pyrimidine nucleoside phosphorylase. The monomer of APRT consists of two domains, alpha and alpha/beta. domain. The alpha domain is a small four-helix bundle, sandwiched next to two additional helices. The alpha/beta-domain consists of eight alpha-helices and one mixed sheet, 5 parallel strands and two anti-parallel alpha strands. The active site of APRT is located at the cleft between the alpha domain and the alpha/beta domain where the trapped MnPPi complex is located. With APRT solved, the structures of all the enzymes and regulatory proteins of tryptophan biosynthesis are now known, the first biosynthetic pathway so delineated.

PUBLICATIONS (resulting from this training, and some recent ones)

Spraggon G, Kim C, Nguyen-Huu X, Yee MC, Yanofsky C, Mills SE. (2001) The structures of anthranilate synthase of Serratia marcescens crystallized in the presence of (i) its substrates, chorismate and glutamine, and a product, glutamate, and (ii) its end-product inhibitor, L-tryptophan. Proc Natl Acad Sci USA. 98:6021-6.

Kim C, Xuong NH, Edwards S, Madhusudan, Yee MC, Spraggon G, Mills SE. (2002) The crystal structure of anthranilate phosphoribosyltransferase from the enterobacterium Pectobacterium carotovorum. FEBS Lett. 523:239-46.

Kim C, Xuong NH, Taylor SS. (2005) Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA. Science. 307:690-6.

Gullingsrud J, Kim C, Taylor SS, McCammon JA. (2006) Dynamic binding of PKA regulatory subunit RI alpha. Structure. 14:141-9.

Taylor SS, Kim C, Vigil D, Haste NM, Yang J, Wu J, Anand GS. (2005) Dynamics of signaling by PKA. Biochim Biophys Acta. 1754:25-37.

Kinderman FS, Kim C, von Daake S, Ma Y, Pham BQ, Spraggon G, Xuong NH, Jennings PA, Taylor SS. (2006) A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase. Mol Cell. 24:397-408.