PDBsum entry 2o4z

Lyase

PDB id: 2o4z

Contents

Protein chain

256 a.a. *

Ligands

HSW

Metals

_ZN

_HG

Waters ×162

* Residue conservation analysis

PDB id:

2o4z

Name:

Lyase

Title:

Crystal structure of the carbonic anhydrase ii complexed with hydroxysulfamide 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

Resolution:

2.10Å R-factor: 0.210 R-free: 0.266

Authors:

C.Temperini,J.Y.Winum,J.L.Montero,A.Scozzafava,C.T.Supuran

Key ref:

C.Temperini et al. (2007). Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors. Bioorg Med Chem Lett, 17, 2795-2801. PubMed id: 17346964 DOI: 10.1016/j.bmcl.2007.02.068

Date:

05-Dec-06 Release date: 15-May-07

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 256 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.1.1 - carbonic anhydrase.
• Reaction: 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.2007.02.068

Bioorg Med Chem Lett 17:2795-2801 (2007)

PubMed id: 17346964

Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors.

C.Temperini, J.Y.Winum, J.L.Montero, A.Scozzafava, C.T.Supuran.

ABSTRACT

N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also inhibits other physiologically relevant isoforms, such as the tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34microM). In order to understand the binding of this inhibitor to the enzyme active site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide adduct was resolved. The inhibitor coordinates to the active site zinc ion by the ionized primary amino group, participating in an extended network of hydrogen bonds with amino acid residues Thr199, Thr200 and two water molecules. The additional two hydrogen bonds in which N-hydroxysulfamide bound to hCA II is involved as compared to the corresponding adduct of sulfamide may explain its higher affinity for the enzyme, also providing hints for the design of tight-binding CA inhibitors possessing an organic moiety substituting the NH group in the N-hydroxysulfamide structure.