6XEB

STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH KETONE INHIBITOR (COMPOUND E)

PDB DOI: https://doi.org/10.2210/pdb6XEB/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2020-06-12 Released: 2020-08-12
Deposition Author(s): Klein, D.J., Clausen, D.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.50 Å
R-Value Free: 0.193
R-Value Work: 0.172
R-Value Observed: 0.173

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Development of a selective HDAC inhibitor aimed at reactivating the HIV latent reservoir.

Clausen, D.J., Liu, J., Yu, W., Duffy, J.L., Chung, C.C., Myers, R.W., Klein, D.J., Fells, J., Holloway, K., Wu, J., Wu, G., Howell, B.J., Barnard, R.J.O., Kozlowski, J.

(2020) Bioorg Med Chem Lett 30: 127367-127367

PubMed: 32738976 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2020.127367
Primary Citation of Related Structures:
6XEB, 6XEC

PubMed Abstract:
The synthesis and SAR development of a trisubstituted imidazole HDAC inhibitor is described. The compounds were synthesized with high diastereocontrol by leveraging Ellman sulfinyl imine chemistry. Structural elucidation provided insight into binding mode and supported design rational. Pharmacokinetic properties of lead compounds were determined.

Organizational Affiliation

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: [email protected].

Macromolecule Content

Total Structure Weight: 132.7 kDa
Atom Count: 10,437
Modelled Residue Count: 1,102
Deposited Residue Count: 1,128
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Histone deacetylase 2	A, B, C	376	Homo sapiens	Mutation(s): 0 Gene Names: HDAC2 EC: 3.5.1.98 (PDB Primary Data), 3.5.1 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q92769 (Homo sapiens) Explore Q92769 Go to UniProtKB: Q92769
PHAROS: Q92769 GTEx: ENSG00000196591
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q92769
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
V1P (Subject of Investigation/LOI) Query on V1P Download Ideal Coordinates CCD File SDF format, chain FA [auth C] SDF format, chain N [auth A] SDF format, chain V [auth B] MOL2 format, chain FA [auth C] MOL2 format, chain N [auth A] MOL2 format, chain V [auth B] mmCIF format, chain FA [auth C] mmCIF format, chain N [auth A] mmCIF format, chain V [auth B]	FA [auth C], N [auth A], V [auth B]	5-{(1S)-7,7-dihydroxy-1-[(1-methylazetidine-3-carbonyl)amino]nonyl}-2-phenyl-1H-imidazole-4-carboxamide C₂₄ H₃₅ N₅ O₄ MYVMGGDKZVVQFO-SFHVURJKSA-N		Interactions Focus chain FA [auth C] Focus chain N [auth A] Focus chain V [auth B] Interactions & Density Focus chain FA [auth C] Focus chain N [auth A] Focus chain V [auth B]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain DA [auth C] SDF format, chain EA [auth C] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain T [auth B] SDF format, chain U [auth B] MOL2 format, chain DA [auth C] MOL2 format, chain EA [auth C] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] mmCIF format, chain DA [auth C] mmCIF format, chain EA [auth C] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B]	DA [auth C] EA [auth C] K [auth A] L [auth A] M [auth A] DA [auth C], EA [auth C], K [auth A], L [auth A], M [auth A], T [auth B], U [auth B]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain DA [auth C] Focus chain EA [auth C] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain T [auth B] Focus chain U [auth B] Interactions & Density Focus chain DA [auth C] Focus chain EA [auth C] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain T [auth B] Focus chain U [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain AA [auth C] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain P [auth B] SDF format, chain Q [auth B] SDF format, chain X [auth C] SDF format, chain Y [auth C] SDF format, chain Z [auth C] MOL2 format, chain AA [auth C] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain X [auth C] MOL2 format, chain Y [auth C] MOL2 format, chain Z [auth C] mmCIF format, chain AA [auth C] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain P [auth B] mmCIF format, chain Q [auth B] mmCIF format, chain X [auth C] mmCIF format, chain Y [auth C] mmCIF format, chain Z [auth C]	AA [auth C] E [auth A] F [auth A] G [auth A] H [auth A] AA [auth C], E [auth A], F [auth A], G [auth A], H [auth A], P [auth B], Q [auth B], X [auth C], Y [auth C], Z [auth C]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain AA [auth C] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain X [auth C] Focus chain Y [auth C] Focus chain Z [auth C] Interactions & Density Focus chain AA [auth C] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain X [auth C] Focus chain Y [auth C] Focus chain Z [auth C]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain O [auth B] SDF format, chain W [auth C] MOL2 format, chain D [auth A] MOL2 format, chain O [auth B] MOL2 format, chain W [auth C] mmCIF format, chain D [auth A] mmCIF format, chain O [auth B] mmCIF format, chain W [auth C]	D [auth A], O [auth B], W [auth C]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain O [auth B] Focus chain W [auth C] Interactions & Density Focus chain D [auth A] Focus chain O [auth B] Focus chain W [auth C]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain BA [auth C] SDF format, chain CA [auth C] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain R [auth B] SDF format, chain S [auth B] MOL2 format, chain BA [auth C] MOL2 format, chain CA [auth C] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] mmCIF format, chain BA [auth C] mmCIF format, chain CA [auth C] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B]	BA [auth C] CA [auth C] I [auth A] J [auth A] R [auth B] BA [auth C], CA [auth C], I [auth A], J [auth A], R [auth B], S [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain BA [auth C] Focus chain CA [auth C] Focus chain I [auth A] Focus chain J [auth A] Focus chain R [auth B] Focus chain S [auth B] Interactions & Density Focus chain BA [auth C] Focus chain CA [auth C] Focus chain I [auth A] Focus chain J [auth A] Focus chain R [auth B] Focus chain S [auth B]