PDB-7mu3: human carbonic anhydrase 9 mimic with compound

ID or keywords:

Entry

Database: PDB / ID: 7mu3

Title

human carbonic anhydrase 9 mimic with compound

Components

Carbonic anhydrase 2

Keywords

LYASE / human carbonic anhydrase II / drug discovery / privileged scaffolds

Function / homology

Function and homology information

positive regulation of cellular pH reduction / positive regulation of dipeptide transmembrane transport / regulation of monoatomic anion transport / secretion / cyanamide hydratase / cyanamide hydratase activity / arylesterase activity / regulation of chloride transport / Reversible hydration of carbon dioxide / morphogenesis of an epithelium ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.35 Å

Authors

Peat, T.S.

Citation

Journal: Bioorg.Med.Chem.Lett. / Year: 2021
Title: Privileged scaffolds in medicinal chemistry: Studies on pyrazolo[1,5-a]pyrimidines on sulfonamide containing Carbonic Anhydrase inhibitors.
Authors: Gumus, A. / Bozdag, M. / Angeli, A. / Peat, T.S. / Carta, F. / Supuran, C.T. / Selleri, S.

History

Deposition	May 14, 2021	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Aug 25, 2021	Provider: repository / Type: Initial release
Revision 1.1	Oct 18, 2023	Group: Data collection / Refinement description Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	7mu3.cif.gz	133.4 KB	Display	PDBx/mmCIF format
PDB format	pdb7mu3.ent.gz	99.1 KB	Display	PDB format
PDBx/mmJSON format	7mu3.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	7mu3_validation.pdf.gz	733.1 KB	Display	wwPDB validaton report
Full document	7mu3_full_validation.pdf.gz	735.3 KB	Display
Data in XML	7mu3_validation.xml.gz	15.4 KB	Display
Data in CIF	7mu3_validation.cif.gz	23 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/mu/7mu3 ftp://data.pdbj.org/pub/pdb/validation_reports/mu/7mu3	HTTPS FTP

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Related structure data

Related structure data	5g03S S: Starting model for refinement
Similar structure data	5ti0-d 3pjj-d 4e49-d 6e91-d 4jss-d 4q8x-d 1avn-d 6yzw-d 2cbe-d 3kon-d 5llh-d 4ruy-d 4zwy-d 5eh8-d 2h4n-d 6t4n-d 4m2w-d 4q87-d 6sks-d 4qiy-2 Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#49 - Jan 2004 Carbonic Anhydrase similarity (1) #222 - Jun 2018 Proteins and Nanoparticles similarity (1) #134 - Feb 2011 Integrin similarity (1) #172 - Apr 2014 RecA and Rad51 similarity (1) #194 - Feb 2016 Designer Insulins similarity (1) #234 - Jun 2019 MDM2 and Cancer similarity (1) #259 - Jul 2021 Designed Proteins and Citizen Science similarity (1)

Deposited unit

A: Carbonic anhydrase 2

hetero molecules

30.2 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author
Evidence: gel filtration

Unit cell

Length a, b, c (Å)	42.016, 41.612, 72.053
Angle α, β, γ (deg.)	90.000, 103.844, 90.000
Int Tables number	4
Space group name H-M	P12₁1

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Protein , 1 types, 1 molecules A

#1: Protein	Carbonic anhydrase 2 / Carbonate dehydratase II / Carbonic anhydrase C / CAC / Carbonic anhydrase II / CA-II Mass: 29226.859 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CA2 / Production host: Escherichia coli (E. coli) / References: UniProt: P00918, carbonic anhydrase

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Non-polymers , 6 types, 278 molecules

#2: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical	ChemComp-ZOA / ethyl (8R)-7-methyl-3-({[(4-sulfamoylphenyl)methyl]carbamothioyl}amino)pyrazolo[1,5-a]pyrimidine-6-carboxylate Mass: 448.519 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₈H₂₀N₆O₄S₂ / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃H₈O₃
#5: Chemical	ChemComp-IMD / IMIDAZOLE Mass: 69.085 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃H₅N₂
#6: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO₄
#7: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 271 / Source method: isolated from a natural source / Formula: H₂O

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Details

Has ligand of interest	Y

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.09 Å³/Da / Density % sol: 41.22 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop Details: Protein at 5.9 mg/mL; 200 nL plus 200 nL drops with the reservoir being 2.7 M ammonium sulfate and 50 mM Tris buffer at pH 8.2 PH range: 8-8.5

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.953733026981 Å
Detector	Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 3, 2019
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.953733026981 Å / Relative weight: 1
Reflection	Resolution: 1.35→41.61 Å / Num. obs: 52509 / % possible obs: 98.5 % / Redundancy: 6.7 % / CC_1/2: 0.998 / R_merge(I) obs: 0.066 / R_pim(I) all: 0.027 / Net I/σ(I): 16.2
Reflection shell	Resolution: 1.35→1.37 Å / R_merge(I) obs: 0.412 / Mean I/σ(I) obs: 3.6 / Num. unique obs: 2048 / CC_1/2: 0.9 / R_pim(I) all: 0.205 / % possible all: 78.6

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0267	refinement
XDS		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 5g03

5g03

Resolution: 1.35→40.829 Å / Cor.coef. F_o:F_c: 0.981 / Cor.coef. F_o:F_c free: 0.971 / SU B: 1.491 / SU ML: 0.028 / Cross valid method: FREE R-VALUE / ESU R: 0.051 / ESU R Free: 0.046
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.1475	2575	4.906 %
R_work	0.1192	49917	-
all	0.121	-	-
obs	-	52492	98.486 %

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT

Displacement parameters

B_iso mean: 15.42 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.032 Å²	0 Å²	0.625 Å²
2-	-	-0.157 Å²	-0 Å²
3-	-	-	-0.163 Å²

Refinement step

Cycle: LAST / Resolution: 1.35→40.829 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2060	0	57	271	2388

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.01	0.013	2375
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.017	2176
X-RAY DIFFRACTION	r_angle_refined_deg	1.651	1.658	3255
X-RAY DIFFRACTION	r_angle_other_deg	1.456	1.603	5063
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.83	5	299
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	36.142	24.159	113
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	13.275	15	391
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	20.302	15	7
X-RAY DIFFRACTION	r_chiral_restr	0.089	0.2	283
X-RAY DIFFRACTION	r_gen_planes_refined	0.009	0.02	2777
X-RAY DIFFRACTION	r_gen_planes_other	0.003	0.02	531
X-RAY DIFFRACTION	r_nbd_refined	0.291	0.2	508
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.206	0.2	2035
X-RAY DIFFRACTION	r_nbtor_refined	0.173	0.2	1066
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.081	0.2	1026
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.235	0.2	175
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.319	0.2	5
X-RAY DIFFRACTION	r_metal_ion_refined	0.076	0.2	4
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.54	0.2	17
X-RAY DIFFRACTION	r_nbd_other	0.2	0.2	61
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.159	0.2	40
X-RAY DIFFRACTION	r_mcbond_it	1.616	1.338	1145
X-RAY DIFFRACTION	r_mcbond_other	1.602	1.335	1144
X-RAY DIFFRACTION	r_mcangle_it	2.101	2.013	1461
X-RAY DIFFRACTION	r_mcangle_other	2.101	2.015	1462
X-RAY DIFFRACTION	r_scbond_it	2.204	1.633	1230
X-RAY DIFFRACTION	r_scbond_other	2.199	1.626	1219
X-RAY DIFFRACTION	r_scangle_it	2.623	2.337	1794
X-RAY DIFFRACTION	r_scangle_other	2.614	2.323	1777
X-RAY DIFFRACTION	r_lrange_it	3.168	27.017	10527
X-RAY DIFFRACTION	r_lrange_other	3.027	26.52	10301
X-RAY DIFFRACTION	r_rigid_bond_restr	1.493	3	4551

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
1.35-1.385	0.216	158	0.192	3027	X-RAY DIFFRACTION	81.6248
1.385-1.423	0.196	201	0.161	3508	X-RAY DIFFRACTION	98.2517
1.423-1.464	0.152	184	0.137	3559	X-RAY DIFFRACTION	99.9733
1.464-1.509	0.149	169	0.105	3439	X-RAY DIFFRACTION	99.9723
1.509-1.559	0.148	169	0.103	3338	X-RAY DIFFRACTION	100
1.559-1.613	0.133	179	0.092	3210	X-RAY DIFFRACTION	99.9705
1.613-1.674	0.124	123	0.097	3144	X-RAY DIFFRACTION	100
1.674-1.743	0.155	164	0.098	2972	X-RAY DIFFRACTION	99.9044
1.743-1.82	0.132	155	0.099	2866	X-RAY DIFFRACTION	100
1.82-1.909	0.113	113	0.096	2792	X-RAY DIFFRACTION	99.9656
1.909-2.012	0.138	130	0.1	2593	X-RAY DIFFRACTION	100
2.012-2.134	0.13	108	0.107	2514	X-RAY DIFFRACTION	100
2.134-2.281	0.125	119	0.103	2341	X-RAY DIFFRACTION	100
2.281-2.464	0.134	135	0.11	2171	X-RAY DIFFRACTION	99.9133
2.464-2.699	0.146	115	0.123	1973	X-RAY DIFFRACTION	99.8565
2.699-3.016	0.158	105	0.133	1824	X-RAY DIFFRACTION	100
3.016-3.482	0.16	93	0.131	1589	X-RAY DIFFRACTION	99.7036
3.482-4.262	0.13	71	0.121	1370	X-RAY DIFFRACTION	99.7232
4.262-6.016	0.179	52	0.142	1076	X-RAY DIFFRACTION	100
6.016-40.829	0.216	32	0.192	611	X-RAY DIFFRACTION	99.5356

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