PDBsum entry 5llh

Lyase

PDB id: 5llh

Contents

Protein chain

257 a.a.

Ligands

V49

DMS ×2

MES

BCN

Metals

_ZN

Waters ×156

PDB id:

5llh

Name:

Lyase

Title:

Crystal structure of human carbonic anhydrase isozyme ii with 4-(1,3- benzothiazol-2-ylthio)-2,3,5,6-tetrafluorobenzenesulfonamide

Structure:

Carbonic anhydrase 2. Chain: a. Fragment: human carbonic anhydrase ii. 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: 469008.

Resolution:

1.90Å R-factor: 0.188 R-free: 0.242

Authors:

E.Manakova,A.Smirnov,S.Grazulis

Key ref:

A.Smirnov et al. (2018). Crystal structure correlations with the intrinsic thermodynamics of human carbonic anhydrase inhibitor binding. PeerJ, 6, e4412. PubMed id: 29503769

Date:

27-Jul-16 Release date: 16-Aug-17

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

PeerJ 6:e4412 (2018)

PubMed id: 29503769

Crystal structure correlations with the intrinsic thermodynamics of human carbonic anhydrase inhibitor binding.

A.Smirnov, A.Zubrienė, E.Manakova, S.Gražulis, D.Matulis.

ABSTRACT

The structure-thermodynamics correlation analysis was performed for a series of fluorine- and chlorine-substituted benzenesulfonamide inhibitors binding to several human carbonic anhydrase (CA) isoforms. The total of 24 crystal structures of 16 inhibitors bound to isoforms CA I, CA II, CA XII, and CA XIII provided the structural information of selective recognition between a compound and CA isoform. The binding thermodynamics of all structures was determined by the analysis of binding-linked protonation events, yielding the intrinsic parameters, i.e., the enthalpy, entropy, and Gibbs energy of binding. Inhibitor binding was compared within structurally similar pairs that differ by para- or meta-substituents enabling to obtain the contributing energies of ligand fragments. The pairs were divided into two groups. First, similar binders-the pairs that keep the same orientation of the benzene ring exhibited classical hydrophobic effect, a less exothermic enthalpy and a more favorable entropy upon addition of the hydrophobic fragments. Second, dissimilar binders-the pairs of binders that demonstrated altered positions of the benzene rings exhibited the non-classical hydrophobic effect, a more favorable enthalpy and variable entropy contribution. A deeper understanding of the energies contributing to the protein-ligand recognition should lead toward the eventual goal of rational drug design where chemical structures of ligands could be designed based on the target protein structure.