PDBsum entry 4zs3

Fluorescent protein/inhibitor

PDB id: 4zs3

Contents

Protein chain

432 a.a.

Ligands

AKG

A4F

Metals

_MN

Waters ×52

PDB id:

4zs3

Name:

Fluorescent protein/inhibitor

Title:

Structural complex of 5-aminofluorescein bound to the fto protein

Structure:

Alpha-ketoglutarate-dependent dioxygenase fto. Chain: a. Fragment: unp residues 32-505. Synonym: fat mass and obesity-associated protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fto, kiaa1752. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.45Å R-factor: 0.209 R-free: 0.263

Authors:

T.Wang,T.Hong,Y.Huang,C.G.Yang,X.Zhou

Key ref:

T.Wang et al. (2015). Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein. J Am Chem Soc, 137, 13736-13739. PubMed id: 26457839 DOI: 10.1021/jacs.5b06690

Date:

13-May-15 Release date: 04-Nov-15

Protein chain

Q9C0B1  (FTO_HUMAN) -  Alpha-ketoglutarate-dependent dioxygenase FTO from Homo sapiens

Seq: 505 a.a.

Struc: 432 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.1.14.11.- - ?????
• Enzyme class 2: E.C.1.14.11.53 - mRNA N(6)-methyladenine demethylase.
• Reaction: an N₆-methyladenosine in mRNA + 2-oxoglutarate + O2 = an adenosine in mRNA + formaldehyde + succinate + CO2

N(6)-methyladenosine in mRNA (Bound ligand (Het Group name = AKG) corresponds exactly) + 2-oxoglutarate + O2 = adenosine in mRNA + formaldehyde + succinate + CO2

• Cofactor: Fe(3+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/jacs.5b06690

J Am Chem Soc 137:13736-13739 (2015)

PubMed id: 26457839

Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein.

T.Wang, T.Hong, Y.Huang, H.Su, F.Wu, Y.Chen, L.Wei, W.Huang, X.Hua, Y.Xia, J.Xu, J.Gan, B.Yuan, Y.Feng, X.Zhang, C.G.Yang, X.Zhou.

ABSTRACT

The FTO protein is unequivocally reported to play a critical role in human obesity and in the regulation of cellular levels of m(6)A modification, which makes FTO a significant and worthy subject of study. Here, we identified that fluorescein derivatives can selectively inhibit FTO demethylation, and the mechanisms behind these activities were elucidated after we determined the X-ray crystal structures of FTO/fluorescein and FTO/5-aminofluorescein. Furthermore, these inhibitors can also be applied to the direct labeling and enrichment of FTO protein combined with photoaffinity labeling assay.