6PM9: Core catalytic domain of human O-GlcNAcase

Crystal structure of the core catalytic domain of human O-GlcNAcase bound to MK-8719. Determined by X-ray diffraction at 2.86 Å resolution. Released 18 Sept 2019.

Method: X-ray diffraction
Resolution: 2.86 Å
Organism: Homo sapiens
Chains: 8
Atoms: 13,916
Mol. weight: 250.69 kDa
Ligands: OQ1
Released: 18 Sept 2019

Explore 6PM9 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6PM9 contains 77 α-helices and 42 β-strands across 8 chains. 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: 15 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	61-66	6	1
α-helix	72-74	3
α-helix	75-87	13
β-strand	92-95	4	1
α-helix	109-111	3
α-helix	113-128	16
β-strand	132-137	6	1
α-helix	148-162	15
β-strand	168-172	5	1
α-helix	179-181	3
α-helix	182-187	6
α-helix	191-205	15
β-strand	212-215	4	1
α-helix	232-240	9
β-strand	246-249	4	1
β-strand	259	1	2
α-helix	261-271	11
α-helix	274-275	2
β-strand	276-279	4	1
β-strand	299	1	2
α-helix	304-306	3
β-strand	309-312	4	1
α-helix	318-321	4
α-helix	322-333	12
α-helix	376-390	15
β-strand	395	1	3

Chain B: 14 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	61-66	6	4
α-helix	72-74	3
α-helix	75-87	13
β-strand	92-95	4	4
α-helix	109-112	4
α-helix	113-128	16
β-strand	132-137	6	4
α-helix	148-162	15
β-strand	168-172	5	4
α-helix	182-187	6
α-helix	191-205	15
β-strand	212-215	4	4
α-helix	221-223	3
α-helix	232-240	9
β-strand	246-249	4	4
β-strand	259	1	5
α-helix	261-270	10
β-strand	276-279	4	4
β-strand	299	1	5
α-helix	301-306	6
β-strand	309-312	4	4
α-helix	318-321	4
α-helix	322-334	13
α-helix	376-390	15
β-strand	395	1	6

Chain C: 14 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	61-66	6	7
α-helix	75-87	13
β-strand	92-95	4	7
α-helix	110-111	2
α-helix	113-128	16
β-strand	132-137	6	7
α-helix	148-162	15
β-strand	168-172	5	7
α-helix	182-185	4
α-helix	191-205	15
β-strand	212-215	4	7
α-helix	221-223	3
α-helix	232-240	9
β-strand	246-249	4	7
α-helix	261-271	11
α-helix	274-275	2
β-strand	276-279	4	7
α-helix	304-306	3
β-strand	309-312	4	7
α-helix	319-321	3
α-helix	322-333	12
α-helix	376-389	14

Chain D: 13 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	61-66	6	8
α-helix	75-87	13
β-strand	92-95	4	8
α-helix	101-105	5
α-helix	113-128	16
β-strand	132-137	6	8
α-helix	148-162	15
β-strand	168-172	5	8
α-helix	183-187	5
α-helix	191-205	15
β-strand	212-215	4	8
α-helix	232-240	9
α-helix	245	1
β-strand	246-249	4	8
α-helix	261-270	10
β-strand	276-279	4	8
α-helix	301-306	6
β-strand	309-312	4	8
α-helix	318-321	4
α-helix	322-333	12
α-helix	376-389	14

Chain E: 5 helices, 0 β-strands

Element	Residues	Length
α-helix	555-564	10
α-helix	573-586	14
α-helix	604-629	26
α-helix	635-657	23
α-helix	684-690	7

Chain F: 5 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	555-564	10
α-helix	573-586	14
α-helix	604-629	26
β-strand	633	1	3
α-helix	634-658	25
α-helix	684-690	7

Chain G: 6 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	555-564	10
α-helix	573-586	14
α-helix	604-628	25
β-strand	633	1	6
α-helix	634-650	17
α-helix	652-658	7
α-helix	684-690	7

Chain H: 5 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	555-564	10
β-strand	567	1	9
β-strand	570	1	9
α-helix	573-586	14
α-helix	607-628	22
α-helix	634-659	26
α-helix	684-690	7

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
O-GlcNAcase TIM-barrel domain	A, B, C, D	protein	388	Homo sapiens	O60502 (AlphaFold model)
O-GlcNAcase stalk domain	E, F, G, H	protein	161	Homo sapiens	O60502 (AlphaFold model)

Sequence of entity 1 (A, B, C, D), FASTA

>6PM9_1 O-GlcNAcase TIM-barrel domain (chains A, B, C, D)
GESELSSNPAASAGASLEPPAAPAPGEDNPAGAGGAAVAGAAGGARRFLCGVVEGFYGRP
WVMEQRKELFRRLQKWELNTYLYAPKDDYKHRMFWREMYSVEEAEQLMTLISAAREYEIE
FIYAISPGLDITFSNPKEVSTLKRKLDQVSQFGCRSFALLFDDIDHNMCAADKEVFSSFA
HAQVSITNEIYQYLGEPETFLFCPTEYCGTFCYPNVSQSPYLRTVGEKLLPGIEVLWTGP
KVVSKEIPVESIEEVSKIIKRAPVIWDNIHANDYDQKRLFLGPYKGRSTELIPRLKGVLT
NPNCEFEANYVAIHTLATWYKSNMNGVRKDVVMTDSEDSTVSIQIKLENEGSDEDIETDV
LYSPQMALKLALTEWLQEFGVPHQYSSR

Sequence of entity 2 (E, F, G, H), FASTA

>6PM9_2 O-GlcNAcase stalk domain (chains E, F, G, H)
MTLEDLQLLADLFYLPYEHGPKGAQMLREFQWLRANSSVVSVNCKGKDSEKIEEWRSRAA
KFEEMCGLVMGMFTRLSNCANRTILYDMYSYVWDIKSIMSMVKSFVQWLGCRSHSSAQFL
IGDQEPWAFRGGLAGEFQRLLPIDGANDLFFQPHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
OQ1	(3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3aH-py…	C9 H14 F2 N2 O3 S	4

Primary citation

Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies. Selnick, H.G., Hess, J.F., Tang, C. et al. J Med Chem (2019) 62:10062-10097. DOI 10.1021/acs.jmedchem.9b01090 · PubMed

Other PDB entries of the same protein (UniProt O60502 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5UN8 2.13 Å, Crystal Structure of human O-GlcNAcase in complex with glycopeptide p53
5M7U 2.3 Å, Structure of human O-GlcNAc hydrolase with new iminocyclitol type inhibitor
11LJ 2.33 Å, Human oga in complex with ligand 24
5M7R 2.35 Å, Structure of human O-GlcNAc hydrolase
5M7S 2.4 Å, Structure of human O-GlcNAc hydrolase with bound transition state analog ThiametG
7OU6 2.41 Å, Human O-GlcNAc hydrolase in complex with DNJNAc-thiazolidines
5TKE 2.48 Å, Crystal Structure of Eukaryotic Hydrolase
5UN9 2.5 Å, The crystal structure of human O-GlcNAcase in complex with Thiamet-G
8P0L 2.5 Å, Crystal structure of human O-GlcNAcase in complex with an S-linked CKII peptide
9BA8 2.54 Å, O-GlcNAcase (OGA) inhibitor complex for the Treatment of Alzheimer's Disease
2YDQ 2.6 Å, CpOGA D298N in complex with hOGA-derived O-GlcNAc peptide
5M7T 2.6 Å, Structure of human O-GlcNAc hydrolase with PugNAc type inhibitor

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