PDBsum entry 2hoc

Lyase

PDB id

2hoc

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Contents

			Protein chain

					258 a.a. *

			Ligands

					1CN ×2


					MBO


					GOL

			Metals

					_ZN

			Waters ×161

* Residue conservation analysis

PDB id:

2hoc

Links

Name:

Lyase

Title:

Crystal structure of the human carbonic anhydrase ii in complex with the 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole- 2-sulfonamide inhibitor

Structure:

Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Ec: 4.2.1.1

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: human erythrocytes

Resolution:

2.10Å

R-factor:

0.184

R-free:

0.223

Authors:

V.Menchise,A.Di Fiore,G.De Simone

Key ref:

V.Menchise et al. (2006). Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II. Bioorg Med Chem Lett, 16, 6204-6208. PubMed id: 17000110 DOI: 10.1016/j.bmcl.2006.09.022

Date:

14-Jul-06

Release date:

10-Oct-06

PROCHECK

	Headers

	References

Protein chain

P00918 (CAH2_HUMAN) - Carbonic anhydrase 2 from Homo sapiens

Seq: Struc:					260 a.a. 258 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.4.2.1.1 - carbonic anhydrase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

hydrogencarbonate + H⁺ = CO2 + H2O

hydrogencarbonate	+	H(+)	=	CO2	+	H2O

Cofactor:

Zn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.bmcl.2006.09.022	Bioorg Med Chem Lett 16:6204-6208 (2006)
PubMed id: 17000110

Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II.
V.Menchise, G.De Simone, A.Di Fiore, A.Scozzafava, C.T.Supuran.

ABSTRACT

The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the two compounds binds in the canonic manner to the zinc ion and interacts with Thr199, Glu106, and Thr200. The substituted phenyl tail of the second inhibitor was positioned in the hydrophobic part of the binding pocket, at van der Waals distance from Phe131, Val 135, Val141, Leu198, Pro202, and Leu204. These structures may help in the design of better inhibitors of these widespread zinc-containing enzymes.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21354674

J.Liu, D.Obando, V.Liao, T.Lifa, and R.Codd (2011).
The many faces of the adamantyl group in drug design.

Eur J Med Chem, 46, 1949-1963.

20157916

H.Park, S.Kim, Y.E.Kim, and S.J.Lim (2010).
A structure-based virtual screening approach toward the discovery of histone deacetylase inhibitors: identification of promising zinc-chelating groups.

ChemMedChem, 5, 591-597.

18335973

V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.

Chem Rev, 108, 946.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.