The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism
Since the discovery of its role in vitamin D metabolism, significant progress has been made in the understanding of gene organisation, protein structure, catalytic function, and genetic polymorphism of cytochrome P450 2R1 (CYP2R1). Located on chromosome 11p15.2, CYP2R1 possesses five exons, unlike m...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31305 |
| _version_ | 1797716812766380032 |
|---|---|
| author | Amelia Nathania Dong Boon Hooi Tan Yan Pan Chin Eng Ong |
| author_facet | Amelia Nathania Dong Boon Hooi Tan Yan Pan Chin Eng Ong |
| author_sort | Amelia Nathania Dong |
| collection | DOAJ |
| description | Since the discovery of its role in vitamin D metabolism, significant progress has been made in the understanding of gene organisation, protein structure, catalytic function, and genetic polymorphism of cytochrome P450 2R1 (CYP2R1). Located on chromosome 11p15.2, CYP2R1 possesses five exons, unlike most other CYP isoforms that carry nine exons. CYP2R1 crystal structure displays a fold pattern typical of a CYP protein, with 12 a-helices as its structural core, and b-sheets mostly arranged on one side, and the heme buried in the interior part of the protein. Overall, CYP2R1 structure adopts a closed conformation with the B′ helix serving as a gate covering the substrate access channel, with the substrate vitamin D3 occupying a position with the side chain pointing toward the heme group. In liver, CYP2R1 25-hydroxylates vitamin D and serves as an important determinant of 25(OH)D level in the tissue and in circulation. While substrate profile has been well studied, inhibitor specificity for CYP2R1 requires further investigation. Both exonic and non-exonic single nucleotide polymorphisms (SNPs) have been reported in CYP2R1, including the CYP2R1*2 carrying Leu99Pro exchange, and a number of non-exonic SNPs with variable functional consequences in gene regulation. A non-exonic SNP, rs10741657, has its causal relationship with diseases established, including that of rickets, ovarian cancer, and multiple sclerosis. The role of other CYP2R1 SNPs in vitamin D deficiency and their causal link to other traits however remain uncertain currently and more studies are warranted to help identify possible physiological mechanisms underlying those complex traits. |
| first_indexed | 2024-03-12T08:27:06Z |
| format | Article |
| id | doaj.art-b47450a71af4493e94b255595e2061a9 |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2024-03-12T08:27:06Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-b47450a71af4493e94b255595e2061a92023-09-02T18:03:53ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262021-02-012410.18433/jpps31305The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic PolymorphismAmelia Nathania DongBoon Hooi TanYan PanChin Eng Ong0Monash University MalaysiaSince the discovery of its role in vitamin D metabolism, significant progress has been made in the understanding of gene organisation, protein structure, catalytic function, and genetic polymorphism of cytochrome P450 2R1 (CYP2R1). Located on chromosome 11p15.2, CYP2R1 possesses five exons, unlike most other CYP isoforms that carry nine exons. CYP2R1 crystal structure displays a fold pattern typical of a CYP protein, with 12 a-helices as its structural core, and b-sheets mostly arranged on one side, and the heme buried in the interior part of the protein. Overall, CYP2R1 structure adopts a closed conformation with the B′ helix serving as a gate covering the substrate access channel, with the substrate vitamin D3 occupying a position with the side chain pointing toward the heme group. In liver, CYP2R1 25-hydroxylates vitamin D and serves as an important determinant of 25(OH)D level in the tissue and in circulation. While substrate profile has been well studied, inhibitor specificity for CYP2R1 requires further investigation. Both exonic and non-exonic single nucleotide polymorphisms (SNPs) have been reported in CYP2R1, including the CYP2R1*2 carrying Leu99Pro exchange, and a number of non-exonic SNPs with variable functional consequences in gene regulation. A non-exonic SNP, rs10741657, has its causal relationship with diseases established, including that of rickets, ovarian cancer, and multiple sclerosis. The role of other CYP2R1 SNPs in vitamin D deficiency and their causal link to other traits however remain uncertain currently and more studies are warranted to help identify possible physiological mechanisms underlying those complex traits.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31305 |
| spellingShingle | Amelia Nathania Dong Boon Hooi Tan Yan Pan Chin Eng Ong The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism Journal of Pharmacy & Pharmaceutical Sciences |
| title | The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism |
| title_full | The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism |
| title_fullStr | The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism |
| title_full_unstemmed | The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism |
| title_short | The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism |
| title_sort | cyp2r1 enzyme structure function enzymatic properties and genetic polymorphism |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31305 |
| work_keys_str_mv | AT amelianathaniadong thecyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism AT boonhooitan thecyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism AT yanpan thecyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism AT chinengong thecyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism AT amelianathaniadong cyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism AT boonhooitan cyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism AT yanpan cyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism AT chinengong cyp2r1enzymestructurefunctionenzymaticpropertiesandgeneticpolymorphism |