PDBsum entry 4mlx

Lyase

PDB id: 4mlx

Contents

Protein chain

257 a.a.

Ligands

MBO

TM7

DMS

Metals

_ZN

Waters ×190

PDB id:

4mlx

Name:

Lyase

Title:

Structure of a bidentate 3-hydroxy-4h-pyran-4-thione ligand bound to hcaii

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:

1.65Å R-factor: 0.159 R-free: 0.200

Authors:

D.P.Martin,S.M.Cohen

Key ref:

D.P.Martin et al. (2014). 'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site. J Am Chem Soc, 136, 5400-5406. PubMed id: 24635441 DOI: 10.1021/ja500616m

Date:

06-Sep-13 Release date: 02-Jul-14

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 257 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.1.1 - carbonic anhydrase.
• Reaction: hydrogencarbonate + H⁺ = CO2 + H2O
• Cofactor: Zn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/ja500616m

J Am Chem Soc 136:5400-5406 (2014)

PubMed id: 24635441

'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

D.P.Martin, P.G.Blachly, A.R.Marts, T.M.Woodruff, C.A.de Oliveira, J.A.McCammon, D.L.Tierney, S.M.Cohen.

ABSTRACT

The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.