| RRC ID |
72246
|
| 著者 |
Kim SY, Mori T, Chek MF, Furuya S, Matsumoto K, Yajima T, Ogura T, Hakoshima T.
|
| タイトル |
Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family.
|
| ジャーナル |
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.
|
| 巻・号 |
11(1)
|
| ページ |
2120
|
| 公開日 |
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
|
| リソース情報 |
| 遺伝子材料 |
pGEXM (VAT1, Full-length) (RDB19564)
pGEXM (VAT1, 37-393) (RDB19565)
pGEXM (VAT1, 43-393) (RDB19566) |
