Effects of copper occupancy on the conformational landscape of peptidylglycine α-hydroxylating monooxygenase

Sweta Maheshwari, Chizu Shimokawa, Katarzyna Rudzka, Chelsey D. Kline, Betty A. Eipper, Richard E. Mains, Sandra B. Gabelli, Ninian Blackburn, L. Mario Amzel

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The structures of metalloproteins that use redox-active metals for catalysis are usually exquisitely folded in a way that they are prearranged to accept their metal cofactors. Peptidylglycine α-hydroxylating monooxygenase (PHM) is a dicopper enzyme that catalyzes hydroxylation of the α-carbon of glycine-extended peptides for the formation of des-glycine amidated peptides. Here, we present the structures of apo-PHM and of mutants of one of the copper sites (H107A, H108A, and H172A) determined in the presence and absence of citrate. Together, these structures show that the absence of one copper changes the conformational landscape of PHM. In one of these structures, a large interdomain rearrangement brings residues from both copper sites to coordinate a single copper (closed conformation) indicating that full copper occupancy is necessary for locking the catalytically competent conformation (open). These data suggest that in addition to their required participation in catalysis, the redox-active metals play an important structural role.

Original languageEnglish (US)
Article number74
JournalCommunications Biology
Volume1
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Fingerprint Dive into the research topics of 'Effects of copper occupancy on the conformational landscape of peptidylglycine α-hydroxylating monooxygenase'. Together they form a unique fingerprint.

Cite this