Reference - Detail
| RRC ID | 72246 |
|---|---|
| Author | Kim SY, Mori T, Chek MF, Furuya S, Matsumoto K, Yajima T, Ogura T, Hakoshima T. |
| Title | Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family. |
| Journal | Sci Rep |
| Abstract |
Vesicle amine transport protein-1 (VAT-1) has been implicated in the regulation of vesicular transport, mitochondrial fusion, phospholipid transport and cell migration, and is a potential target of anticancer drugs. Little is known about the molecular function of VAT-1. The amino acid sequence indicates that VAT-1 belongs to the quinone oxidoreductase subfamily, suggesting that VAT-1 may possess enzymatic activity in unknown redox processes. To clarify the molecular function of VAT-1, we determined the three-dimensional structure of human VAT-1 in the free state at 2.3 Å resolution and found that VAT-1 forms a dimer with the conserved NADPH-binding cleft on each protomer. We also determined the structure of VAT-1 in the NADP-bound state at 2.6 Å resolution and found that NADP binds the binding cleft to create a putative active site with the nicotine ring. Substrate screening suggested that VAT-1 possesses oxidoreductase activity against quinones such as 1,2-naphthoquinone and 9,10-phenanthrenequinone. |
| Volume | 11(1) |
| Pages | 2120 |
| Published | 2021-1-22 |
| DOI | 10.1038/s41598-021-81409-y |
| PII | 10.1038/s41598-021-81409-y |
| PMID | 33483563 |
| PMC | PMC7822847 |
| MeSH | Binding Sites / genetics Biocatalysis Catalytic Domain Crystallography, X-Ray Humans Kinetics Models, Molecular NAD(P)H Dehydrogenase (Quinone) / chemistry* NAD(P)H Dehydrogenase (Quinone) / genetics NAD(P)H Dehydrogenase (Quinone) / metabolism NADP / chemistry NADP / metabolism Protein Binding Protein Domains* Protein Multimerization* Substrate Specificity Vesicular Transport Proteins / chemistry* Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism |
| IF | 3.998 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pGEXM (VAT1, Full-length) (RDB19564) pGEXM (VAT1, 37-393) (RDB19565) pGEXM (VAT1, 43-393) (RDB19566) |