PDBsum entry 7k6t

Lyase/lyase inhibitor

PDB id: 7k6t

Contents

Protein chain

257 a.a.

Ligands

VYV

GOL

Metals

_ZN

Waters ×147

PDB id:

7k6t

Name:

Lyase/lyase inhibitor

Title:

Carbonic anhydrase ix mimic complexed with 4-(2-(3-phenylureido) ethylsulfonamido)benzenesulfonamide

Structure:

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

Source:

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

Resolution:

1.76Å R-factor: 0.182 R-free: 0.212

Authors:

J.T.Andring,S.Singh,R.Mckenna

Key ref:

O.Akgul et al. (2021). Handling drug-target selectivity: A study on ureido containing Carbonic Anhydrase inhibitors. Eur J Med Chem, 212, 113035. PubMed id: 33303238 DOI: 10.1016/j.ejmech.2020.113035

Date:

21-Sep-20 Release date: 23-Dec-20

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 257 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

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.ejmech.2020.113035

Eur J Med Chem 212:113035 (2021)

PubMed id: 33303238

Handling drug-target selectivity: A study on ureido containing Carbonic Anhydrase inhibitors.

O.Akgul, S.Singh, J.T.Andring, R.McKenna, S.Selleri, F.Carta, A.Angeli, C.T.Supuran.

ABSTRACT

Here we report the synthesis of a series of taurine substituted sulfonamide derivatives 1-29 having the ureido moiety installed at the tail section as selective inhibitors of the tumor associated human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) IX and XII. The series was deeply investigated for their kinetic features which demonstrated a strong dependence on the ureido moiety. High resolution X-ray crystallographic investigation on selected ligand adducts complexed with hCA II and hCA IX-mimic revealed a strong correlation between the ureido moiety and the amino acid residues Q92 and Q67 in both the hCA II and hCA IX-mimic, contributing to highly stabilized ligand-protein complex.