PDBsum entry 2cbb

Lyase(oxo-acid)

PDB id: 2cbb

Contents

Protein chain

258 a.a. *

Metals

_ZN

Waters ×220

* Residue conservation analysis

PDB id:

2cbb

Name:

Lyase(oxo-acid)

Title:

Structure of native and apo carbonic anhydrase ii and some of its anion-ligand complexes

Structure:

Carbonic anhydrase ii. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606

Resolution:

1.67Å R-factor: 0.153

Authors:

K.Hakansson,M.Carlsson,L.A.Svensson,A.Liljas

Key ref:

K.Håkansson et al. (1992). Structure of native and apo carbonic anhydrase II and structure of some of its anion-ligand complexes. J Mol Biol, 227, 1192-1204. PubMed id: 1433293 DOI: 10.1016/0022-2836(92)90531-N

Date:

01-Jun-92 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: 10.1016/0022-2836(92)90531-N

J Mol Biol 227:1192-1204 (1992)

PubMed id: 1433293

Structure of native and apo carbonic anhydrase II and structure of some of its anion-ligand complexes.

K.Håkansson, M.Carlsson, L.A.Svensson, A.Liljas.

ABSTRACT

In order to obtain a better structural framework for understanding the catalytic mechanism of carbonic anhydrase, a number of inhibitor complexes of the enzyme were investigated crystallographically. The three-dimensional structure of free human carbonic anhydrase II was refined at pH 7.8 (1.54 A resolution) and at pH 6.0 (1.67 A resolution). The structure around the zinc ion was identical at both pH values. The structure of the zinc-free enzyme was virtually identical with that of the native enzyme, apart from a water molecule that had moved 0.9 A to fill the space that would be occupied by the zinc ion. The complexes with the anionic inhibitors bisulfite and formate were also studied at neutral pH. Bisulfite binds with one of its oxygen atoms, presumably protonized, to the zinc ion and replaces the zinc water. Formate, lacking a hydroxyl group, is bound with its oxygen atoms not far away from the position of the non-protonized oxygen atoms of the bisulfite complex, i.e. at hydrogen bond distance from Thr199 N and at a position between the zinc ion and the hydrophobic part of the active site. The result of these and other studies have implications for our view of the catalytic function of the enzyme, since virtually all inhibitors share some features with substrate, product or expected transition states. A reaction scheme where electrophilic activation of carbon dioxide plays an important role in the hydration reaction is presented. In the reverse direction, the protonized oxygen of the bicarbonate is forced upon the zinc ion, thereby facilitating cleavage of the carbon-oxygen bond. This is achieved by the combined action of the anionic binding site, which binds carboxyl groups, the side-chain of threonine 199, which discriminates between hydrogen bond donors and acceptors, and hydrophobic interaction between substrate and the active site cavity. The required proton transfer between the zinc water and His64 can take place through water molecules 292 and 318.

Selected figure(s)

Figure 1.
Figure 1. The molecules involved in he hydrogen bond chain between His64 an the zinc water molecule in native carbnic anhydrase at pH 7%. Distances and angles are; 64Nd' -2920HH-3180HH: (322 A. 196.7''. 2.73 A) and 2920HH-3180HH-2630HH: (2.7 A, lOS.l'', 2.79 A).

Figure 3.
Figure 3. A larger view than in Fig. 2 of the active site. Note the ydrophobic nature of the right hand sde of the cleft ith valins 121, 143 and 207, leucines 141 and 198 and tryptophan 209.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 227, 1192-1204) copyright 1992.

Figures were selected by an automated process.