PDBsum entry 4rux

Lyase

PDB id: 4rux

Contents

Protein chain

257 a.a.

Ligands

3W3 ×2

GOL

Metals

_ZN

Waters ×239

PDB id:

4rux

Name:

Lyase

Title:

Crystal structure of human carbonic anhydrase ii in complex with 4- (allyloxy)benzenesulfonamide

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.14Å R-factor: 0.152 R-free: 0.162

Authors:

M.A.Pinard,R.Mckenna

Key ref:

F.Carta et al. (2015). A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects. Bioorg Med Chem Lett, 23, 1828-1840. PubMed id: 25766630 DOI: 10.1016/j.bmc.2015.02.027

Date:

23-Nov-14 Release date: 22-Apr-15

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 257 a.a.

Enzyme reactions

• Enzyme class 2: E.C.4.2.1.1 - carbonic anhydrase.
• Reaction: hydrogencarbonate + H⁺ = CO2 + H2O
• Cofactor: Zn(2+)
• Enzyme class 3: E.C.4.2.1.69 - cyanamide hydratase.
• Reaction: urea = cyanamide + H2O

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1016/j.bmc.2015.02.027

Bioorg Med Chem Lett 23:1828-1840 (2015)

PubMed id: 25766630

A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects.

F.Carta, L.Di Cesare Mannelli, M.Pinard, C.Ghelardini, A.Scozzafava, R.McKenna, C.T.Supuran.

ABSTRACT

A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) of which multiple isoforms are known, and some appear to be involved in pain. These sulfonamides showed modest inhibition against the cytosolic isoform CA I, but were generally effective, low nanomolar CA II, VII, IX and XII inhibitors. X-ray crystallographic data for the adduct of several such sulfonamides with CA II allowed us to rationalize the good inhibition data. In a mice model of neuropathic pain induced by oxaliplatin, one of the strong CA II/VII inhibitors reported here induced a long lasting pain relieving effect, a fact never observed earlier. This is the first report of rationally designed sulfonamide CA inhibitors with pain effective modulating effects.