PDBsum entry 4hmh

Transferase

PDB id: 4hmh

Contents

Protein chains

161 a.a.

47 a.a.

Ligands

SO4 ×2

GOL

F94

PEG

Metals

_ZN

Waters ×39

PDB id:

4hmh

Name:

Transferase

Title:

Crystal structure of tankyrase 2 in complex with 7,3-dihydroxyflavone

Structure:

Tankyrase-2. Chain: a. Fragment: c-terminal fragment, unp residues 946-1113. Synonym: tank2, adp-ribosyltransferase diphtheria toxin-like 6, artd6, poly [adp-ribose] polymerase 5b, tnks-2, trf1-interacting ankyrin-related adp-ribose polymerase 2, tankyrase ii, tankyrase-like protein, tankyrase-related protein. Engineered: yes. Tankyrase-2.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tnks2, parp5b, tank2, tnkl. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.30Å R-factor: 0.214 R-free: 0.262

Authors:

M.Narwal,T.Haikarainen,L.Lehtio

Key ref:

M.Narwal et al. (2013). Screening and structural analysis of flavones inhibiting tankyrases. J Med Chem, 56, 3507-3517. PubMed id: 23574272 DOI: 10.1021/jm3018783

Date:

18-Oct-12 Release date: 31-Oct-12

Protein chain

Q9H2K2  (TNKS2_HUMAN) -  Poly [ADP-ribose] polymerase tankyrase-2 from Homo sapiens

Seq: 1166 a.a.

Struc: 161 a.a.

Protein chain

Q9H2K2  (TNKS2_HUMAN) -  Poly [ADP-ribose] polymerase tankyrase-2 from Homo sapiens

Seq: 1166 a.a.

Struc: 47 a.a.

Enzyme reactions

• Enzyme class 2: Chains A, C: E.C.2.4.2.- - ?????
• Enzyme class 3: Chains A, C: E.C.2.4.2.30 - NAD(+) ADP-ribosyltransferase.

Pathway:

• Reaction: NAD⁺ + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D- ribosyl)n+1-acceptor + H⁺

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

Added reference

DOI no: 10.1021/jm3018783

J Med Chem 56:3507-3517 (2013)

PubMed id: 23574272

Screening and structural analysis of flavones inhibiting tankyrases.

M.Narwal, T.Haikarainen, A.Fallarero, P.M.Vuorela, L.Lehtiö.

ABSTRACT

Flavonoids are known for their beneficial effects on human health, and therefore the therapeutic potential of these compounds have been extensively studied. Flavone has been previously identified as a tankyrase inhibitor, and to further elucidate whether tankyrases would be inhibited by other flavonoids, we performed a systematic screening of tankyrase 2 inhibitory activity using 500 natural and naturally derived flavonoids covering nine different flavonoid classes. All identified tankyrase inhibitors were flavones. We report crystal structures of all the hit compounds in complex with the catalytic domain of human tankyrase 2. Flavone derivatives in all 10 crystal structures bind to the nicotinamide binding site of tankyrase 2. Potencies of the active flavones toward tankyrases vary between 50 nM and 1.1 μM, and flavones show up to 200-fold selectivity for tankyrases over ARTD1. The molecular details of the interactions revealed by cocrystal structures efficiently describe the properties of potent flavone derivatives inhibiting tankyrases.