3GCL: Mode Of Ligand Binding And Assignment Of Subsites In Mammalian Peroxidases: Crystal Structure Of Lactoperoxidase Complexes With Acetyl Salycylic Acid, Salicylhydroxamic Acid And Benzylhydroxamic Acid

Citation:
Abstract
The binding and structural studies of bovine lactoperoxidase with three aromatic ligands, acetylsalicylic acid (ASA), salicylhydoxamic acid (SHA), and benzylhydroxamic acid (BHA) show that all the three compounds bind to lactoperoxidase at the substrate binding site on the distal heme side. The binding of ASA occurs without perturbing the position of conserved heme water molecule W-1, whereas both SHA and BHA displace it by the hydroxyl group of their hydroxamic acid moieties. The acetyl group carbonyl oxygen atom of ASA forms a hydrogen bond with W-1, which in turn makes three other hydrogen-bonds, one each with heme iron, His-109 N(epsilon2), and Gln-105 N(epsilon2). In contrast, in the complexes of SHA and BHA, the OH group of hydroxamic acid moiety in both complexes interacts with heme iron directly with Fe-OH distances of 3.0 and 3.2A respectively. The OH is also hydrogen bonded to His-109 N(epsilon2) and Gln-105N(epsilon2). The plane of benzene ring of ASA is inclined at 70.7 degrees from the plane of heme moiety, whereas the aromatic planes of SHA and BHA are nearly parallel to the heme plane with inclinations of 15.7 and 6.2 degrees , respectively. The mode of ASA binding provides the information about the mechanism of action of aromatic substrates, whereas the binding characteristics of SHA and BHA indicate the mode of inhibitor binding.
PDB ID: 3GCLDownload
MMDB ID: 70578
PDB Deposition Date: 2009/2/22
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 3GCL: monomeric; determined by author and by software (PISA)
Molecular Components in 3GCL
Label Count Molecule
Protein (1 molecule)
1
Lactoperoxidase(Gene symbol: LPO)
Molecule annotation
Chemicals (22 molecules)
1
1
2
1
3
8
4
2
5
1
6
1
7
8
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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