3FW3

Crystal Structure of soluble domain of CA4 in complex with Dorzolamide

PDB DOI: https://doi.org/10.2210/pdb3FW3/pdb

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

Deposited: 2009-01-16 Released: 2009-12-01
Deposition Author(s): Greasley, S.E., Ferre, R.A.A., Paz, R., Wickersham, J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.72 Å
R-Value Free: 0.206
R-Value Work: 0.176
R-Value Observed: 0.177

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 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: 61.88 kDa
Atom Count: 4,287
Modelled Residue Count: 504
Deposited Residue Count: 532
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	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 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ETS Query on ETS Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain H [auth B] MOL2 format, chain D [auth A] MOL2 format, chain H [auth B] mmCIF format, chain D [auth A] mmCIF format, chain H [auth B]	D [auth A], H [auth B]	(4S-TRANS)-4-(ETHYLAMINO)-5,6-DIHYDRO-6-METHYL-4H-THIENO(2,3-B)THIOPYRAN-2-SULFONAMIDE-7,7-DIOXIDE C₁₀ H₁₆ N₂ O₄ S₃ IAVUPMFITXYVAF-XPUUQOCRSA-N		Interactions Focus chain D [auth A] Focus chain H [auth B] Interactions & Density Focus chain D [auth A] Focus chain H [auth B]
GLC Query on GLC Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	alpha-D-glucopyranose C₆ H₁₂ O₆ WQZGKKKJIJFFOK-DVKNGEFBSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B]	F [auth A], I [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain F [auth A] Focus chain I [auth B] Interactions & Density Focus chain F [auth A] Focus chain I [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain G [auth B] MOL2 format, chain C [auth A] MOL2 format, chain G [auth B] mmCIF format, chain C [auth A] mmCIF format, chain G [auth B]	C [auth A], G [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain G [auth B] Interactions & Density Focus chain C [auth A] Focus chain G [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
SO4	BindingDB: 3FW3	Ki: min: 9.00e+6, max: 4.40e+7 (nM) from 2 assay(s)
ETS	BindingDB: 3FW3	Ki: min: 43, max: 8530 (nM) from 3 assay(s)
	BindingDB: 3FW3	IC50: min: 32, max: 43 (nM) from 2 assay(s)
	PDBBind: 3FW3	IC50: 43 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.72 Å
R-Value Free: 0.206
R-Value Work: 0.176
R-Value Observed: 0.177
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 49.991	α = 90
b = 70.826	β = 91.91
c = 71.774	γ = 90

Software Package:

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

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-12-01

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2009-12-01
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Data collection, Derived calculations, Structure summary
Version 1.3: 2023-09-06
Changes: Data collection, Database references, Refinement description, Structure summary
Version 1.4: 2024-11-06
Changes: Structure summary