3F7U

Crystal Structure of soluble domain of CA4 in complex with small molecule.

PDB DOI: https://doi.org/10.2210/pdb3F7U/pdb

Classification: LYASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2008-11-10 Released: 2009-09-22
Deposition Author(s): Pauly, T.A., Ferre, R.A.A., Greasley, S.E., Paz, R.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.264
R-Value Work: 0.212
R-Value Observed: 0.214

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation.

Vernier, W., Chong, W., Rewolinski, D., Greasley, S., Pauly, T., Shaw, M., Dinh, D., Ferre, R.A., Nukui, S., Ornelas, M., Reyner, E.

(2010) Bioorg Med Chem 18: 3307-3319

PubMed: 20363633 Search on PubMed
DOI: https://doi.org/10.1016/j.bmc.2010.03.014
Primary Citation of Related Structures:
3F7B, 3F7U, 3FW3

PubMed Abstract:
A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure-activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate.

Organizational Affiliation

Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, CA 92121, USA. [email protected]

Macromolecule Content

Total Structure Weight: 123.25 kDa
Atom Count: 8,351
Modelled Residue Count: 988
Deposited Residue Count: 1,064
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Carbonic anhydrase 4	A, B, C, D	266	Homo sapiens	Mutation(s): 0 Gene Names: CA4 EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P22748 (Homo sapiens) Explore P22748 Go to UniProtKB: P22748
PHAROS: P22748 GTEx: ENSG00000167434
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P22748
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
AG4 Query on AG4 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]	N-(3-methoxypropyl)-2-(phenylsulfanyl)-5-sulfamoylpyridine-3-carboxamide C₁₆ H₁₉ N₃ O₄ S₂ YFGZGDDAWQULRR-UHFFFAOYSA-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]
ZN Query on ZN 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]	ZINC ION Zn PTFCDOFLOPIGGS-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
AG4	PDBBind: 3F7U	IC50: 246 (nM) from 1 assay(s)
AG4	BindingDB: 3F7U	IC50: 246 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.264
R-Value Work: 0.212
R-Value Observed: 0.214
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 64.886	α = 90
b = 123.83	β = 90
c = 152.723	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data collection
REFMAC	refinement
HKL-2000	data reduction
HKL-2000	data scaling
REFMAC	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-09-22

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2009-09-22
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2023-12-27
Changes: Data collection, Database references, Derived calculations
Version 1.3: 2024-04-03
Changes: Refinement description