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3'-Phosphoadenosine-5'-phosphosulfate reductase in complex with thioredoxin: a structural snapshot in the catalytic cycle

Academic Article
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Overview

authors

  • Chartron, J.
  • Shiau, C.
  • Stout, C. David
  • Carroll, Kate

publication date

  • April 2007

journal

  • Biochemistry  Journal

abstract

  • The crystal structure of Escherichia coli 3'-phosphoadenosine-5'-phosphosulfate (PAPS) reductase in complex with E. coli thioredoxin 1 (Trx1) has been determined to 3.0 A resolution. The two proteins are covalently linked via a mixed disulfide that forms during nucleophilic attack of Trx's N-terminal cysteine on the Sgamma atom of the PAPS reductase S-sulfocysteine (E-Cys-Sgamma-SO3-), a central intermediate in the catalytic cycle. For the first time in a crystal structure, residues 235-244 in the PAPS reductase C-terminus are observed, depicting an array of interprotein salt bridges between Trx and the strictly conserved glutathione-like sequence, Glu238Cys239Gly240Leu241His242. The structure also reveals a Trx-binding surface adjacent to the active site cleft and regions of PAPS reductase associated with conformational change. Interaction at this site strategically positions Trx to bind the S-sulfated C-terminus and addresses the mechanism for requisite structural rearrangement of this domain. An apparent sulfite-binding pocket at the protein-protein interface explicitly orients the S-sulfocysteine Sgamma atom for nucleophilic attack in a subsequent step. Taken together, the structure of PAPS reductase in complex with Trx highlights the large structural rearrangement required to accomplish sulfonucleotide reduction and suggests a role for Trx in catalysis beyond the paradigm of disulfide reduction.

subject areas

  • Amino Acid Sequence
  • Binding Sites
  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli
  • Models, Molecular
  • Oxidoreductases
  • Thioredoxins
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Identity

PubMed Central ID

  • PMC3109433

International Standard Serial Number (ISSN)

  • 0006-2960

Digital Object Identifier (DOI)

  • 10.1021/bi700130e

PubMed ID

  • 17352498
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Additional Document Info

start page

  • 3942

end page

  • 3951

volume

  • 46

issue

  • 13

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