4NMH

11-beta-HSD1 in complex with a 3,3-Di-methyl-azetidin-2-one

PDB DOI: https://doi.org/10.2210/pdb4NMH/pdb

Classification: oxidoreductase/oxidoreductase INHIBITOR
Organism(s): Mus musculus
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2013-11-15 Released: 2014-03-26
Deposition Author(s): McCoull, W., Augustin, M., Blake, C., Ertan, A., Kilgour, E.K., Krapp, S., Moore, J.E., Newcombe, N.J., Packer, M.J., Rees, A., Revill, J., Scott, J.S., Selmi, N., Gerhardt, S., Ogg, D.J., Steinbacher, S., Whittamore, P.R.O.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.90 ?
R-Value Free: 0.251
R-Value Work: 0.199
R-Value Observed: 0.201

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Identification and optimisation of 3,3-dimethyl-azetidin-2-ones as potent and selective inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1)

McCoull, W., Augustin, M., Blake, C., Ertan, A., Kilgour, E.K., Krapp, S., Moore, J.E., Newcombe, N.J., Packer, M.J., Rees, A., Revill, J., Scott, J.S., Selmi, N., Gerhardt, S., Ogg, D.J., Steinbacher, S., Whittamore, P.R.O.

To be published.

Macromolecule Content

Total Structure Weight: 136.62 kDa
Atom Count: 8,506
Modelled Residue Count: 1,058
Deposited Residue Count: 1,184
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Corticosteroid 11-beta-dehydrogenase isozyme 1	A, B, C, D	296	Mus musculus	Mutation(s): 3 Gene Names: Hsd11b1, Hsd11 EC: 1.1.1.146 (PDB Primary Data), 1.1.1.201 (UniProt)
UniProt
Find proteins for P50172 (Mus musculus) Explore P50172 Go to UniProtKB: P50172
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P50172
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NDP Query on NDP Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] SDF format, chain M [auth C] SDF format, chain Q [auth D] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] MOL2 format, chain M [auth C] MOL2 format, chain Q [auth D] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B] mmCIF format, chain M [auth C] mmCIF format, chain Q [auth D]	F [auth A], I [auth B], M [auth C], Q [auth D]	NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₃₀ N₇ O₁₇ P₃ ACFIXJIJDZMPPO-NNYOXOHSSA-N		Interactions Focus chain F [auth A] Focus chain I [auth B] Focus chain M [auth C] Focus chain Q [auth D] Interactions & Density Focus chain F [auth A] Focus chain I [auth B] Focus chain M [auth C] Focus chain Q [auth D]
2KG Query on 2KG Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain L [auth C] SDF format, chain P [auth D] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain L [auth C] MOL2 format, chain P [auth D] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B] mmCIF format, chain L [auth C] mmCIF format, chain P [auth D]	E [auth A], H [auth B], L [auth C], P [auth D]	(4S)-4-(2-methoxyphenyl)-3,3-dimethyl-1-[3-(methylsulfonyl)phenyl]azetidin-2-one C₁₉ H₂₁ N O₄ S JTEHJTAGXBHCOJ-KRWDZBQOSA-N		Interactions Focus chain E [auth A] Focus chain H [auth B] Focus chain L [auth C] Focus chain P [auth D] Interactions & Density Focus chain E [auth A] Focus chain H [auth B] Focus chain L [auth C] Focus chain P [auth D]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain J [auth B] SDF format, chain K [auth B] SDF format, chain N [auth C] SDF format, chain O [auth C] SDF format, chain R [auth D] MOL2 format, chain G [auth A] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] MOL2 format, chain N [auth C] MOL2 format, chain O [auth C] MOL2 format, chain R [auth D] mmCIF format, chain G [auth A] mmCIF format, chain J [auth B] mmCIF format, chain K [auth B] mmCIF format, chain N [auth C] mmCIF format, chain O [auth C] mmCIF format, chain R [auth D]	G [auth A] J [auth B] K [auth B] N [auth C] O [auth C] G [auth A], J [auth B], K [auth B], N [auth C], O [auth C], R [auth D]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain N [auth C] Focus chain O [auth C] Focus chain R [auth D] Interactions & Density Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain N [auth C] Focus chain O [auth C] Focus chain R [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.90 ?
R-Value Free: 0.251
R-Value Work: 0.199
R-Value Observed: 0.201
Space Group: P 1 2₁ 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 96.132	α = 90
b = 70.842	β = 91.67
c = 95.653	γ = 90

Software Package:

Software Name	Purpose
ADSC	data collection
MOLREP	phasing
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-03-26

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2014-03-26
Type: Initial release
Version 1.1: 2024-02-28
Changes: Data collection, Database references, Derived calculations, Refinement description