The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis

Yoshimitsu Kakuta, Evgeny V. Petrotchenko, Lars C. Pedersen, Masahiko Negishi

Research output: Contribution to journalArticle

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Abstract

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)- E2 complex 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.

Original languageEnglish
Pages (from-to)27325-27330
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number42
DOIs
Publication statusPublished - Oct 16 1998
Externally publishedYes

Fingerprint

Vanadates
Crystal structure
Molecules
Phenol
Phosphoadenosine Phosphosulfate
Phosphates
Oxygen
Water
Catalysis
estrone sulfotransferase
Estradiol
Steroids
Mutation
Geometry

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis. / Kakuta, Yoshimitsu; Petrotchenko, Evgeny V.; Pedersen, Lars C.; Negishi, Masahiko.

In: Journal of Biological Chemistry, Vol. 273, No. 42, 16.10.1998, p. 27325-27330.

Research output: Contribution to journalArticle

Kakuta, Yoshimitsu ; Petrotchenko, Evgeny V. ; Pedersen, Lars C. ; Negishi, Masahiko. / The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 42. pp. 27325-27330.
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abstract = "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)- E2 complex 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-{\AA} 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 {\AA}) and a possible water molecule (2.3 {\AA}). 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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