PDBsum entry 5nxp

Lyase

PDB id: 5nxp

Contents

Protein chain

258 a.a.

Ligands

9DH

Metals

_ZN

Waters ×285

PDB id:

5nxp

Name:

Lyase

Title:

Carbonic anhydrase ii inhibitor ra7

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:

1.25Å R-factor: 0.129 R-free: 0.162

Authors:

J.Brynda,P.Rezacova,M.Horejsi,J.Fanfrlik

Key ref:

A.Pecina et al. (2018). Ranking Power of the SQM/COSMO Scoring Function on Carbonic Anhydrase II-Inhibitor Complexes. Chemphyschem, 19, 873-879. PubMed id: 29316128 DOI: 10.1002/cphc.201701104

Date:

10-May-17 Release date: 17-Jan-18

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 258 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: 10.1002/cphc.201701104

Chemphyschem 19:873-879 (2018)

PubMed id: 29316128

Ranking Power of the SQM/COSMO Scoring Function on Carbonic Anhydrase II-Inhibitor Complexes.

A.Pecina, J.Brynda, L.Vrzal, R.Gnanasekaran, M.Hořejší, S.M.Eyrilmez, J.Řezáč, M.Lepšík, P.Řezáčová, P.Hobza, P.Majer, V.Veverka, J.Fanfrlík.

ABSTRACT

Accurate prediction of protein-ligand binding affinities is essential for hit-to-lead optimization and virtual screening. The reliability of scoring functions can be improved by including quantum effects. Here, we demonstrate the ranking power of the semiempirical quantum mechanics (SQM)/implicit solvent (COSMO) scoring function by using a challenging set of 10 inhibitors binding to carbonic anhydrase II through Zn²⁺ in the active site. This new dataset consists of the high-resolution (1.1-1.4 Å) crystal structures and experimentally determined inhibitory constant (K_i ) values. It allows for evaluation of the common approximations, such as representing the solvent implicitly or by using a single target conformation combined with a set of ligand docking poses. SQM/COSMO attained a good correlation of R² of 0.56-0.77 with the experimental inhibitory activities, benefiting from careful handling of both noncovalent interactions (e.g. charge transfer) and solvation. This proof-of-concept study of SQM/COSMO ranking for metalloprotein-ligand systems demonstrates its potential for hit-to-lead applications.