PDBsum entry 4x63

Transferase/transferase inhibitor

PDB id: 4x63

Contents

Protein chains

625 a.a.

309 a.a.

Ligands

SAH

3XV

Waters ×1

PDB id:

4x63

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of prmt5:mep50 with epz015666 and sah

Structure:

Protein arginine n-methyltransferase 5. Chain: a. Synonym: 72 kda icln-binding protein,histone-arginine n- methyltransferase prmt5,jak-binding protein 1,shk1 kinase-binding protein 1 homolog,skb1hs. Engineered: yes. Methylosome protein 50. Chain: b. Synonym: mep-50,androgen receptor cofactor p44,wd repeat-containing

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: prmt5, hrmt1l5, ibp72, jbp1, skb1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Gene: wdr77, mep50, wd45, hkmt1069, nbla10071.

Resolution:

3.05Å R-factor: 0.217 R-free: 0.274

Authors:

P.A.Boriack-Sjodin

Key ref:

E.Chan-Penebre et al. (2015). A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol, 11, 432-437. PubMed id: 25915199 DOI: 10.1038/nchembio.1810

Date:

06-Dec-14 Release date: 22-Apr-15

Protein chain

O14744  (ANM5_HUMAN) -  Protein arginine N-methyltransferase 5 from Homo sapiens

Seq: 637 a.a.

Struc: 625 a.a.

Protein chain

Q9BQA1  (MEP50_HUMAN) -  Methylosome protein WDR77 from Homo sapiens

Seq: 342 a.a.

Struc: 309 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.2.1.1.320 - type Ii protein arginine methyltransferase.
• Reaction: L-arginyl-[protein] + 2 S-adenosyl-L-methionine = N(omega),N(omega)'-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L- homocysteine + 2 H⁺

L-arginyl-[protein] (Bound ligand (Het Group name = SAH) matches with 96.30% similarity) + 2 × S-adenosyl-L-methionine = N(omega),N(omega)'-dimethyl-L-arginyl-[protein] + 2 × S-adenosyl-L- homocysteine + 2 × H(+)

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

Added reference

DOI no: 10.1038/nchembio.1810

Nat Chem Biol 11:432-437 (2015)

PubMed id: 25915199

A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models.

E.Chan-Penebre, K.G.Kuplast, C.R.Majer, P.A.Boriack-Sjodin, T.J.Wigle, L.D.Johnston, N.Rioux, M.J.Munchhof, L.Jin, S.L.Jacques, K.A.West, T.Lingaraj, K.Stickland, S.A.Ribich, A.Raimondi, M.P.Scott, N.J.Waters, R.M.Pollock, J.J.Smith, O.Barbash, M.Pappalardi, T.F.Ho, K.Nurse, K.P.Oza, K.T.Gallagher, R.Kruger, M.P.Moyer, R.A.Copeland, R.Chesworth, K.W.Duncan.

ABSTRACT

No abstract given.