Cofactor-containing antibodies: crystal structure of the original yellow antibody

Proceedings of the National Academy of Sciences of the United States of America
Xueyong ZhuIan A Wilson

Abstract

Antibodies are generally thought to be a class of proteins that function without the use of cofactors. However, it is not widely appreciated that antibodies are believed to be the major carrier protein in human circulation for the important riboflavin cofactor that is involved in a host of biological phenomena. A further link between riboflavin and antibodies was discovered 30 years ago when a bright-yellow antibody, IgG(GAR), was purified from a patient with multiple myeloma who had turned yellow during the course of her disease. It was subsequently shown that the yellow color of this antibody was due to riboflavin binding. However, it was not known how and where riboflavin was bound to this antibody. We now report the crystal structure of this historically important IgG(GAR) Fab at 3.0-A resolution. The riboflavin is located in the antigen-combining site with its isoalloxazine ring stacked between the parallel aromatic moieties of TyrH33, PheH58, and TyrH100A. Together with additional hydrogen bonds, these interactions reveal the structural basis for high-affinity riboflavin binding. The ligand specificity of IgG(GAR) is compared with another riboflavin-binding antibody, IgG(DOT), which was purified from a second patient with...Continue Reading

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Citations

May 9, 2012·PloS One·Iftekhar HassanImrana Naseem
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yang XuKim D Janda
Sep 23, 2014·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Imrana NaseemSandesh Chibber
Sep 11, 2007·Journal of Pharmaceutical Sciences·Hongcheng LiuJoanne Sun
Apr 3, 2010·Protein Expression and Purification·John P BannantineBrian V Geisbrecht
Mar 10, 2017·Journal of Biomolecular Structure & Dynamics·Md Maroof AlamImrana Naseem
Jan 8, 2015·The Journal of Biological Chemistry·Maxime LecerfJordan D Dimitrov
Nov 1, 2016·Nutrition and Cancer·Iftekhar HassanIbrahim M Alhazza
Feb 6, 2019·Nature Reviews. Immunology·Alexia KanyavuzJordan D Dimitrov
Oct 15, 2010·Proceedings·Robert Arthur Kyle, William Clifford Roberts
Nov 2, 2019·Journal of Pharmaceutical Sciences·Alison WallaceMichael J Treuheit
Jun 3, 2021·Antibodies·Alexandre Ambrogelly

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