Journal of Biological Chemistry
Volume 273, Issue 42, 16 October 1998, Pages 27325-27330
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ENZYMOLOGY
The Sulfuryl Transfer Mechanism: CRYSTAL STRUCTURE OF A VANADATE COMPLEX OF ESTROGEN SULFOTRANSFERASE AND MUTATIONAL ANALYSIS*

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Estrogen sulfotransferase (EST) catalyzes transfer of the 5′-sulfuryl group of adenosine 3′-phosphate 5′-phosphosulfate (PAPS) to the 3α-phenol group of estrogenic steroids such as estradiol (E2). The recent crystal structure of EST-adenosine 3′,5′-diphosphate (PAP)- E2complex has revealed that residues Lys48, Thr45, Thr51, Thr52, Lys106, His108, and Try240 are in position to play a catalytic role in the sulfuryl transfer reaction of EST (Kakuta Y., Pedersen, L. G., Carter, C. W., Negishi, M., and Pedersen, L. C. (1997) Nat. Struct. Biol. 4, 904–908). Mutation of Lys48, Lys106, or His108 nearly abolishes EST activity, indicating that they play a critical role in catalysis. A present 2.2-Å resolution structure of EST-PAP-vanadate complex indicates that the vanadate molecule adopts a trigonal bipyramidal geometry with its equatorial oxygens coordinated to these three residues. The apical positions of the vanadate molecule are occupied by a terminal oxygen of the 5′-phosphate of PAP (2.1 Å) and a possible water molecule (2.3 Å). This water molecule superimposes well to the 3α-phenol group of E2 in the crystal structure of the EST·PAP·E2 complex. These structures are characteristic of the transition state for an in-line sulfuryl transfer reaction from PAPS to E2. Moreover, residues Lys48, Lys106, and His108 are found to be coordinated with the vanadate molecule at the transition state of EST.

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The atomic coordinates and structure factors (for EST + PaP, 1bo2; for EST + PAP + E 2 , 1bo3; for EST + PAP + VO 4 , 1bo3) have been deposited in the Protein Data Bank, Brookhaven National Laboratory, Upton, NY.

JSPS Research Fellow in Biomedical and Biobehavioral Research at the National Institutes of Health.