Journal
BIOCHEMISTRY
Volume 46, Issue 13, Pages 3942-3951Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi700130e
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI-51622, R01 AI051622] Funding Source: Medline
- NIGMS NIH HHS [R01 GM087638, R01 GM087638-01A1, GM-48870, P01 GM048870] Funding Source: Medline
Ask authors/readers for more resources
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 S gamma atom of the PAPS reductase S-sulfocysteine (E-Cys-S gamma-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, Glu(238)Cys(239)Gly(240)Leu(241)His(242). 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 S gamma 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available