3QQP | pdb_00003qqp

Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Urea Inhibitor

PDB DOI: https://doi.org/10.2210/pdb3QQP/pdb

Classification: OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2011-02-16 Released: 2012-02-22
Deposition Author(s): Loenze, P., Schimanski-Breves, S., Engel, C.K.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.72 Å
R-Value Free:
0.234 (Depositor), 0.240 (DCC)
R-Value Work:
0.164 (Depositor), 0.170 (DCC)
R-Value Observed:
0.168 (Depositor)

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Pyrrolidine-pyrazole ureas as potent and selective inhibitors of 11beta-hydroxysteroid-dehydrogenase type 1.

Venier, O., Pascal, C., Braun, A., Namane, C., Mougenot, P., Crespin, O., Pacquet, F., Mougenot, C., Monseau, C., Onofri, B., Dadji-Faihun, R., Leger, C., Ben-Hassine, M., Van-Pham, T., Ragot, J.L., Philippo, C., Gussregen, S., Engel, C., Farjot, G., Noah, L., Maniani, K., Nicolai, E.

(2011) Bioorg Med Chem Lett 21: 2244-2251

PubMed: 21439819 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2011.02.111
Primary Citation of Related Structures:
3QQP

PubMed Abstract:
A High Throughput Screening campaign allowed the identification of a novel class of ureas as 11β-HSD1 inhibitors. Rational chemical optimization provided potent and selective inhibitors of both human and murine 11β-HSD1 with an appropriate ADME profile and ex vivo activity in target tissues.

Organizational Affiliation

Sanofi-aventis R&D, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin, France. Olivier.Venier@sanofi-aventis.com

Macromolecule Content

Total Structure Weight: 131.57 kDa
Atom Count: 8,650
Modelled Residue Count: 1,056
Deposited Residue Count: 1,144
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	286	Homo sapiens	Mutation(s): 1 Gene Names: HSD11, HSD11B1, HSD11L EC: 1.1.1.146 (PDB Primary Data), 1.1.1.201 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P28845 (Homo sapiens) Explore P28845 Go to UniProtKB: P28845
PHAROS: P28845 GTEx: ENSG00000117594
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P28845
Sequence Annotations Expand
Reference Sequence LOADING

Small Molecules

Ligands 2 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 H [auth B] SDF format, chain J [auth C] SDF format, chain L [auth D] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain L [auth D] mmCIF format, chain F [auth A] mmCIF format, chain H [auth B] mmCIF format, chain J [auth C] mmCIF format, chain L [auth D]	F [auth A], H [auth B], J [auth C], L [auth D]	NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₃₀ N₇ O₁₇ P₃ ACFIXJIJDZMPPO-NNYOXOHSSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D] Interactions & Density Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D]
S05 Query on S05 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth B] SDF format, chain I [auth C] SDF format, chain K [auth D] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] MOL2 format, chain I [auth C] MOL2 format, chain K [auth D] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B] mmCIF format, chain I [auth C] mmCIF format, chain K [auth D]	E [auth A], G [auth B], I [auth C], K [auth D]	3,4-dihydroquinolin-1(2H)-yl[4-(1H-imidazol-5-yl)piperidin-1-yl]methanone C₁₈ H₂₂ N₄ O UTSIHHDNMUZNMG-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D]

Binding Affinity Annotations
ID	Source	Binding Affinity
S05	BindingDB: 3QQP	IC50: 42 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.72 Å
R-Value Free: 0.234 (Depositor), 0.240 (DCC)
R-Value Work: 0.164 (Depositor), 0.170 (DCC)
R-Value Observed: 0.168 (Depositor)

Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 56.927	α = 90
b = 153.385	β = 93.46
c = 74.179	γ = 90

Software Package:

Software Name	Purpose
XSCALE	data scaling
BUSTER-TNT	refinement
PDB_EXTRACT	data extraction
REFMAC	phasing
BUSTER	refinement

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-02-22

Deposition Author(s):

Loenze, P.

Schimanski-Breves, S.

Engel, C.K.

Revision History (Full details and data files)

Version 1.0: 2012-02-22
Type: Initial release
Version 1.1: 2013-05-08
Changes: Database references
Version 1.2: 2017-10-11
Changes: Data collection
Version 1.3: 2024-02-21
Changes: Data collection, Database references, Derived calculations

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Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Urea Inhibitor

Pyrrolidine-pyrazole ureas as potent and selective inhibitors of 11beta-hydroxysteroid-dehydrogenase type 1.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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