PDBsum entry 6i2f

Lyase

PDB id: 6i2f

Contents

Protein chain

257 a.a.

Ligands

MBO

BGC

3W6

Metals

_ZN

_HG ×2

Waters ×282

PDB id:

6i2f

Name:

Lyase

Title:

Human carbonic anhydrase ii in complex with 4- propoxybenzenesulfonamide

Structure:

Carbonic anhydrase 2. Chain: a. Synonym: carbonate dehydratase ii,carbonic anhydrasE C,cac,carbonic anhydrase ii,ca-ii. Engineered: yes. Other_details: the first 5 amino acids (gspef) are remnants of an expression tag.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: codon plus.

Resolution:

1.20Å R-factor: 0.117 R-free: 0.139

Authors:

S.Gloeckner,A.Heine,G.Klebe

Key ref:

S.Glöckner et al. (2020). Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors. ACS Chem Biol, 15, 675-685. PubMed id: 32027480 DOI: 10.1021/acschembio.9b00895

Date:

01-Nov-18 Release date: 20-Nov-19

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: 10.1021/acschembio.9b00895

ACS Chem Biol 15:675-685 (2020)

PubMed id: 32027480

Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.

S.Glöckner, K.Ngo, C.P.Sager, T.Hüfner-Wulsdorf, A.Heine, G.Klebe.

ABSTRACT

Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermodynamic and kinetic data from calorimetric titration measurements. The present study demonstrates the convenient collection of calorimetric data suitable for both thermodynamic and kinetic analysis for two series of congeneric ligands of human carbonic anhydrase II and correlates these findings with structural data obtained by macromolecular crystallography to shed light on the importance of shape complementarity for thermodynamics and kinetics governing a protein-ligand binding event. The study shows how minute chemical alterations change preferred ligand conformation and can be used to manipulate thermodynamic and kinetic signatures of binding. They give rise to the observation that analogous n-alkyl and n-alkyloxy derivatives of identical chain length swap their binding kinetic properties at unchanged binding affinity.