PDBsum entry 5e2r

Lyase

PDB id: 5e2r

Contents

Protein chain

261 a.a.

Ligands

520

GOL

Metals

_ZN

Waters ×267

PDB id:

5e2r

Name:

Lyase

Title:

The crystal structure of the human carbonic anhydrase ii in complex with a 1,1'-biphenyl-4-sulfonamide inhibitor

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 'bl21-gold(de3)plyss ag'. Expression_system_taxid: 866768

Resolution:

1.60Å R-factor: 0.172 R-free: 0.197

Authors:

V.Alterio,G.De Simone

Key ref:

G.La Regina et al. (2015). Discovery of 1,1'-Biphenyl-4-sulfonamides as a New Class of Potent and Selective Carbonic Anhydrase XIV Inhibitors. J Med Chem, 58, 8564-8572. PubMed id: 26497049 DOI: 10.1021/acs.jmedchem.5b01144

Date:

01-Oct-15 Release date: 04-Nov-15

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 261 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: 10.1021/acs.jmedchem.5b01144

J Med Chem 58:8564-8572 (2015)

PubMed id: 26497049

Discovery of 1,1'-Biphenyl-4-sulfonamides as a New Class of Potent and Selective Carbonic Anhydrase XIV Inhibitors.

G.La Regina, A.Coluccia, V.Famiglini, S.Pelliccia, L.Monti, D.Vullo, E.Nuti, V.Alterio, G.De Simone, S.M.Monti, P.Pan, S.Parkkila, C.T.Supuran, A.Rossello, R.Silvestri.

ABSTRACT

New 1,1'-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1-21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1'-biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.