PDBsum entry 1bcd

Lyase(oxo-acid)

PDB id: 1bcd

Contents

Protein chain

258 a.a. *

Ligands

FMS

Metals

_ZN

Waters ×215

* Residue conservation analysis

PDB id:

1bcd

Name:

Lyase(oxo-acid)

Title:

X-ray crystallographic structure of a complex between human carbonic anhydrase ii and a new topical inhibitor, trifluoromethane sulphonamide

Structure:

Carbonic anhydrase ii. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606

Resolution:

1.90Å R-factor: 0.154

Authors:

K.Hakansson,A.Liljas

Key ref:

K.Håkansson and A.Liljas (1994). The structure of a complex between carbonic anhydrase II and a new inhibitor, trifluoromethane sulphonamide. Febs Lett, 350, 319-322. PubMed id: 8070585 DOI: 10.1016/0014-5793(94)00798-5

Date:

31-Aug-93 Release date: 31-Oct-93

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: 10.1016/0014-5793(94)00798-5

Febs Lett 350:319-322 (1994)

PubMed id: 8070585

The structure of a complex between carbonic anhydrase II and a new inhibitor, trifluoromethane sulphonamide.

K.Håkansson, A.Liljas.

ABSTRACT

It has recently been shown that aliphatic sulphonamides are good inhibitors of carbonic anhydrase (CA) provided that the pK of the sulphonamide is low. We have determined the structure of the complex between CAII and CF3SO2NH2 by X-ray crystallographic methods. The nitrogen of the sulphonamide is bound to the zinc ion of the enzyme in the usual manner. The other parts of the inhibitor show a different mode of binding from aromatic sulphonamides since the trifluoromethyl group is bound at the hydrophobic part of the active site instead of pointing out from the active site. It should be possible to design new inhibitors specific for the different isoenzymes, starting from the present structure.

Selected figure(s)

Figure 1.
Fig. 1. (A) The active site of carbonic anhydrase complexed the inhibitor CF3SO2NH-. Difference electron maps were calculated after refinement of native coordinates without waters 263,292, 318,338 and 389. Positive (continous lines) and negative (broken lines) [Fo [ - [ Fc[ contours were drawn at +3 or. (B) The inhibitor from (A) with all atoms labelled.

Figure 2.
Fig. 2. The molecular structure of carbonic anhydrase complexed with is compared with the complex with acetazolamide (broken The polypeptide chain f the acetazolamide complex [251 is not since the conformatons are virtually the same in the two cases.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Febs Lett (1994, 350, 319-322) copyright 1994.