6PAF: Histone-lysine N-methyltransferase SMYD3

Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors. Determined by X-ray diffraction at 1.24 Å resolution. Released 15 Jan 2020.

Method: X-ray diffraction
Resolution: 1.24 Å
Organism: Homo sapiens
Chains: 1
Atoms: 3,935
Mol. weight: 50.77 kDa
Ligands: ZN, MG, SAM, O6A
Released: 15 Jan 2020

Explore 6PAF in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6PAF contains 24 α-helices and 17 β-strands across 1 chain. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 24 helices, 17 β-strands

Element	Residues	Length	Sheet
β-strand	6-10	5	1
β-strand	16-20	5	1
β-strand	24	1	2
β-strand	29-33	5	3
β-strand	37-40	4	4
α-helix	42-44	3
β-strand	48	1	5
β-strand	55	1	5
β-strand	60-61	2	6
α-helix	62	1
β-strand	69-70	2	6
α-helix	73-92	20
α-helix	100-114	15
α-helix	116-118	3
α-helix	119-121	3
α-helix	126-128	3
α-helix	133-135	3
α-helix	138-154	17
α-helix	162-164	3
α-helix	171-181	11
β-strand	183-186	4	4
β-strand	192-197	6	4
α-helix	201-203	3
α-helix	204	1
β-strand	205-206	2	7
β-strand	212-217	6	3
β-strand	220-225	6	3
β-strand	229	1	2
α-helix	233	1
β-strand	234-235	2	1
β-strand	236-237	2	7
α-helix	246-257	12
α-helix	264-268	5
α-helix	272-275	4
α-helix	280-298	19
α-helix	302-313	12
α-helix	325-341	17
α-helix	344-361	18
α-helix	367-382	16
α-helix	386-403	18
α-helix	409-426	18

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histone-lysine N-methyltransferase SMYD3	A	protein	432	Homo sapiens	Q9H7B4 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>6PAF_1 Histone-lysine N-methyltransferase SMYD3 (chains A)
GSFTMEPLKVEKFATANRGNGLRAVTPLRPGELLFRSDPLAYTVCKGSRGVVCDRCLLGK
EKLMRCSQCRVAKYCSAKCQKKAWPDHKRECKCLKSCKPRYPPDSVRLLGRVVFKLMDGA
PSESEKLYSFYDLESNINKLTEDKKEGLRQLVMTFQHFMREEIQDASQLPPAFDLFEAFA
KVICNSFTICNAEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEELT
ICYLDMLMTSEERRKQLRDQYCFECDCFRCQTQDKDADMLTGDEQVWKEVQESLKKIEEL
KAHWKWEQVLAMCQAIISSNSERLPDINIYQLKVLDCAMDACINLGLLEEALFYGTRTME
PYRIFFPGSHPVRGVQVMKVGKLQLHQGMFPQAMKNLRLAFDIMRVTHGREHSLIEDLIL
LLEECDANIRAS

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	3
MG	Magnesium ion	Mg	2
SAM	S-adenosylmethionine	C15 H22 N6 O5 S	1
O6A	N-(1-{[4-(aminomethyl)phenyl]sulfonyl}piperidin-4-yl)-5-cyclopropyl-1,2-oxazole…	C19 H24 N4 O4 S	1

Water and common crystallization additives (GOL) are not listed.

Primary citation

Discovery of Isoxazole Amides as Potent and Selective SMYD3 Inhibitors. Su, D.S., Qu, J., Schulz, M. et al. ACS Med Chem Lett (2020) 11:133-140. DOI 10.1021/acsmedchemlett.9b00493 · PubMed

Other PDB entries of the same protein (UniProt Q9H7B4 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6P7Z 1.19 Å, Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors
5V37 1.42 Å, Crystal structure of SMYD3 with SAM and EPZ028862
5CCL 1.5 Å, Crystal structure of SMYD3 with SAM and oxindole compound
7O2C 1.52 Å, X-RAY STRUCTURE OF SMYD3 IN COMPLEX WITH the benzodiazepine-based probe BAY-6035
3QWP 1.53 Å, Crystal structure of SET and MYND domain containing 3; Zinc finger MYND…
6P6K 1.55 Å, Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors
6ZRB 1.55 Å, Crystal structure of SMYD3 conjugate with piperidine-based covalent inhibitor EM127
7O2A 1.57 Å, X-RAY STRUCTURE OF SMYD3 IN COMPLEX WITH benzodiazepine-type inhibitor compound 15
7QNR 1.57 Å, SMYD3 in complex with fragment FL01791
6O9O 1.59 Å, Crystal Structure of SMYD3 with Potent and Selective Isoxazole Amide Inhibitor 1
6P6G 1.59 Å, Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors
7BJ1 1.61 Å, Crystal structure of SMYD3 with diperodon S enantiomer bound to allosteric site

Browse structure collections

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