Homology modeling of human 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) based on the crystal structure of rabbit CYP2C5

The Journal of Steroid Biochemistry and Molecular Biology
Keiko YamamotoSachiko Yamada

Abstract

Seventeen missense mutations of 25-hydroxyvitamin D(3) 1alpha-hydroxylase (CYP27B1) that cause Vitamin D-dependent rickets type I (VDDR-I) have been identified. To understand the mechanism by which each mutation disrupts 1alpha-hydroxylase activity and to visualize the substrate-binding site, we performed the homology modeling of CYP27B1. The three-dimensional (3D) structure of CYP27B1 was modeled on the basis of the crystal structure of rabbit CYP2C5, the first solved X-ray structure of a eukaryotic CYP. The 3D structure of CYP27B1 contains 17 helices and 6 beta-strands, and the overall structural folding is similar to the available structures of soluble CYPs as well as to the template CYP2C5. Mapping of the residues responsible for VDDR-I has provided much information concerning the function of each mutant. We have previously reported site-directed mutagenesis studies on several mutants of CYP27B1 causing VDDR-1, and suggested the role of each residue. All these suggestions are in good agreement with our 3D-model of CYP27B1. Furthermore, this model enabled us to predict the function of the other mutation residues responsible for VDDR-I.

References

Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·B C ChungW L Miller
Jun 5, 1987·Journal of Molecular Biology·T L PoulosA J Howard
Feb 1, 1995·Nature Structural Biology·J R Cupp-Vickery, T L Poulos
Mar 4, 1994·Journal of Molecular Biology·C A HasemannJ Deisenhofer
Jan 1, 1996·Methods in Enzymology·S E Graham-Lorence, J A Peterson
Oct 23, 1997·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·R St-ArnaudF H Glorieux
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·T ShinkiT Suda
Dec 5, 1998·American Journal of Human Genetics·J T WangW L Miller
Jul 27, 2000·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·A A Portale, W L Miller
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·L M PodustM R Waterman

❮ Previous
Next ❯

Citations

Mar 5, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Edith K Y TangRobert C Tuckey
Jul 14, 2010·Biochimica Et Biophysica Acta·Inge Schuster
Feb 13, 2007·Biochemical and Biophysical Research Communications·Natsumi SawadaToshiyuki Sakaki
Sep 17, 2004·Biochemical and Biophysical Research Communications·Eriko UchidaKuniyo Inouye
May 14, 2008·Clinica Chimica Acta; International Journal of Clinical Chemistry·Indra Ramasamy
Mar 29, 2008·Bioorganic & Medicinal Chemistry·Masayuki HataTyuji Hoshino
Nov 2, 2018·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·Y ChiW Xia
Jun 11, 2010·The Journal of Clinical Endocrinology and Metabolism·Ali S AlzahraniYufei Shi
Sep 15, 2020·Jornal brasileiro de nefrologia : ʹorgão oficial de Sociedades Brasileira e Latino-Americana de Nefrologia·Rachita Singh DhullSrikanta Basu
Jan 7, 2016·Clinical Case Reports·Laila FüchtbauerAnja L Frederiksen
Mar 5, 2008·Biochemistry·Hiroshi SugimotoToshiyuki Sakaki
May 14, 2010·Journal of Chemical Information and Modeling·Toshimasa ItohKeiko Yamamoto

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.