@article{3c3f98c35467477f97a3da8da84e631a,
title = "Testosterone meets albumin-the molecular mechanism of sex hormone transport by serum albumins",
abstract = "Serum albumin is the most abundant protein in mammalian blood plasma and is responsible for the transport of metals, drugs, and various metabolites, including hormones. We report the first albumin structure in complex with testosterone, the primary male sex hormone. Testosterone is bound in two sites, neither of which overlaps with the previously suggested Sudlow site I. We determined the binding constant of testosterone to equine and human albumins by two different methods: tryptophan fluorescence quenching and ultrafast affinity extraction. The binding studies and similarities between residues comprising the binding sites on serum albumins suggest that testosterone binds to the same sites on both proteins. Our comparative analysis of albumin complexes with hormones, drugs, and other biologically relevant compounds strongly suggests interference between a number of compounds present in blood and testosterone transport by serum albumin. We discuss a possible link between our findings and some phenomena observed in human patients, such as low testosterone levels in diabetic patients.",
author = "Czub, {Mateusz P.} and Venkataramany, {Barat S.} and Majorek, {Karolina A.} and Handing, {Katarzyna B.} and Porebski, {Przemyslaw J.} and Beeram, {Sandya R.} and Kyungah Suh and Woolfork, {Ashley G.} and Hage, {David S.} and Shabalin, {Ivan G.} and Wladek Minor",
note = "Funding Information: We thank A. Wlodawer, D. R. Cooper, J. Grembecka, and M. Chruszcz for their critical reading and discussions of the manuscript. This work was supported by NIGMS grants (R01-GM117325, R01-GM117080, R01-GM118619) and federal funds awarded to W. M. by the National Institute of Allergy and Infectious Diseases, National Institutes of Health and the United States Department of Health and Human Services under contract no. HHSN272201200026C and HHSN272201700060C. The work that was conducted by D. S. H. was supported, in part, by the National Institutes of Health under R01-GM044391 and through a faculty seed grant from the University of Nebraska–Lincoln Research Council. We also thank K. Brister, Z. Wawrzak, S. Anderson, and J. Brun-zelle for their assistance in data collection. 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 LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (Grant 085P1000817). Publisher Copyright: {\textcopyright} 2019 The Royal Society of Chemistry.",
year = "2019",
doi = "10.1039/c8sc04397c",
language = "English (US)",
volume = "10",
pages = "1607--1618",
journal = "Chemical Science",
issn = "2041-6520",
publisher = "Royal Society of Chemistry",
number = "6",
}