@article{529c5de418994424b39003faa632125b,
title = "Effects of copper occupancy on the conformational landscape of peptidylglycine α-hydroxylating monooxygenase",
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.",
author = "Sweta Maheshwari and Chizu Shimokawa and Katarzyna Rudzka and Kline, {Chelsey D.} and Eipper, {Betty A.} and Mains, {Richard E.} and Gabelli, {Sandra B.} and Ninian Blackburn and Amzel, {L. Mario}",
note = "Funding Information: This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beam line at Sector 31 of the Advanced Photon Source was provided by Eli Lilly Company, which operates the facility. The Life Science Biomedical Technology Research resource (LSBR) is primarily supported by the National Institute of Health, National Institute of General Medical Sciences (NIGMS) through a Biomedical Technology Research Resource P41 grant (P41GM111244), and by the DOE Office of Biological and Environmental Research (KP1605010). As a National Synchrotron Light Source II facility resource at Brookhaven National Laboratory, work performed at the LSBR is supported in part by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences Program under contract number DE-SC0012704 (KC0401040). This work was supported by NSF Grant (LMA)-MCB-1517522 and NIH grants GM-115214 (NJB) and DK-032949 (BAE and REM). Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s42003-018-0082-y",
language = "English (US)",
volume = "1",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}