@article{1a4ffce444b6455fbe3402ecae57ac68,
title = "Betaine-homocysteine methyltransferase: Zinc in a distorted barrel",
abstract = "Betaine-homocysteine methyl transferase (BHMT) catalyzes the synthesis of methionine from betaine and homocysteine (Hcy), utilizing a zinc ion to activate Hcy. BHMT is a key liver enzyme that is important for homocysteine homeostasis. X-ray structures of human BHMT in its oxidized (Zn-free) and reduced (Zn-replete) forms, the latter in complex with the bisubstrate analog, S(δ-carboxybutyl)-L-homocysteine, were determined at resolutions of 2.15 {\AA} and 2.05 {\AA}. BHMT is a (β/α)8 barrel that is distorted to construct the substrate and metal binding sites. The zinc binding sequences G-V/L-N-C and G-G-C-C are at the C termini of strands β6 and β8. Oxidation to the Cys217-Cys299 disulfide and expulsion of Zn are accompanied by local rearrangements. The structures identify Hcy binding fingerprints and provide a prototype for the homocysteine S-methyltransferase family.",
keywords = "(β/α) barrel, Homocysteine, Methyltransfer, Signature sequences, Thiolate ligands, Zinc",
author = "Evans, {John C.} and Huddler, {Donald P.} and Jiri Jiracek and Carmen Castro and Millian, {Norman S.} and Garrow, {Timothy A.} and Ludwig, {Martha L.}",
note = "The authors thank Dr. Mark Hilgers for his contributions to the development of this research. The authors are grateful to Dr. Jeanne Stuckey for counsel and assistance with data collection during several trips to APS. Portions of this work were performed at the following experimental stations at the Advanced Photon Source at Argonne, IL: IMCA-CAT 17-ID, DND-CAT 5-ID-D, and BioCARS 14-BM-C. We are indebted to the staff at IMCA-CAT, DND-CAT, and BioCARS and would particularly like to thank Drs. Andrew Howard, John Quintana, and Keith Brister for their advice and assistance. The facilities of the Industrial Macromolecular Crystallography Association Collaborative Access Team are supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Illinois Institute of Technology (IIT). The DuPont-Northwestern-Dow Collaborative Access Team Synchrotron Research Center is supported by E.I. DuPont de Nemours and Company, The Dow Chemical Company, the U.S. National Science Foundation (DMR-9304725), and the State of Illinois (1BHE HECA NWU 96). Use of BioCARS Sector 14 was supported by the National Institutes of Health, NCRR (RR07707). Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-102-Eng-38. This research was supported by NIH grants GM16429 (MLL) and DK52501 (TAG) and the Grant Agency of the Czech Republic (B4055003).",
year = "2002",
month = sep,
doi = "10.1016/S0969-2126(02)00796-7",
language = "English (US)",
volume = "10",
pages = "1159--1171",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "9",
}