PDBsum entry 3eft

Lyase

PDB id: 3eft

Contents

Protein chain

256 a.a. *

Ligands

3BS

Metals

_ZN

_HG

Waters ×217

* Residue conservation analysis

PDB id:

3eft

Name:

Lyase

Title:

Crystal structure of the complex between carbonic anhydrase ii and a spin-labeled sulfonamide incorporating tempo moiety

Structure:

Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratase ii, carbonic anhydrasE C, cac. Engineered: yes

Source:

Synthetic: yes. Other_details: chemically synthesized. This sequence occurs naturally in humans(homo sapiens).

Resolution:

1.85Å R-factor: 0.195 R-free: 0.240

Authors:

C.Temperini,A.Cecchi,A.Scozzafava,C.T.Supuran

Key ref:

L.Ciani et al. (2009). Dissecting the inhibition mechanism of cytosolic versus transmembrane carbonic anhydrases by ESR. J Phys Chem B, 113, 13998-14005. PubMed id: 19778001

Date:

10-Sep-08 Release date: 08-Sep-09

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

J Phys Chem B 113:13998-14005 (2009)

PubMed id: 19778001

Dissecting the inhibition mechanism of cytosolic versus transmembrane carbonic anhydrases by ESR.

L.Ciani, A.Cecchi, C.Temperini, C.T.Supuran, S.Ristori.

ABSTRACT

Spin-labeled sulfonamides incorporating TEMPO moieties showed efficient activity as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and, in particular, of the physiologically relevant isoenzymes hCA II, hCA IX, and hCA XIV. Here we report a detailed analysis of this class of inhibitors by means of ESR and X-ray crystallography, in comparison with inhibition tests against all mammalian CA isoforms, CA I-XIV. Local dynamics and structure were manifested in the ESR signal through modulation of internal magnetic anisotropies. Analysis and fitting of the ESR spectra of several spin-labeled sulfonamides with isoforms CA II (cytosolic), CA IX (catalytic domain and full length transmembrane, tumor-associated isoform) and CA XIV (transmembrane isozyme) provided information about polarity and dynamics of specific microenvironments sensed by the nitroxyl group within the active site cavity of these isozymes. The comparison of ESR and crystallographic data of hCA II complexed with one of these inhibitors constitutes a useful tool for the understanding of molecular hindrance and ordering within the enzyme active site, and provides theoretical bases to use these inhibitors for imaging purposes of hypoxic tumors overexpressing the transmembrane isozyme CA IX. Combining the sulfonamide zinc-binding group with the TEMPO moiety thus allowed to dissect the selective inhibition mechanism of different cytosolic and transmembrane carbonic anhydrases.