Glucose Oxidase and Biosensors

 

Family Ties

            Glucose oxidase belongs to the GMC (glucose-methanol-choline) oxidoreductase family of proteins, which are all FAD flavoprotein enzymes.  These enzymes share a number of regions of sequence similarity, as well as a conserved structural topology. In addition to glucose oxidase (EC 1.1.3.4), this family includes a variety of functionally distinct enzymes such as choline dehydrogenase (EC 1.1.99.1), methanol oxidase (EC 1.1.3.13), cellobiose dehydrogenase (EC 1.1.99.18), glucose dehydrogenase (EC 1.1.99.10), and cholesterol oxidase (EC 1.1.3.6).  In general, these enzymes have a FAD-binding N-terminal domain composed of a b/b/a sandwich topology, and a substrate-binding C-terminal domain composed of an a/b sandwich topology.

 

What InterPro Tells Us

P13006 Aspergillus niger glucose oxidase

 

InterPro Domain Architecture

 

InterPro Entry

Signatures

Graphical Match

Method Name

IPR000172

PF00732

GMC_oxred_N

IPR000172

PS00623

GMC_OXRED_1

IPR000172

PS00624

GMC_OXRED_2

IPR007867

PF05199

GMC_oxred_C

IPR012132

PIRSF000137

Alcohol_oxidase

Structural Features

 

 

 

1cf3

1cf3A

 

3.30.560.10.1

1cf3A3   

 

3.50.50.60.15

1cf3A1   

 

4.10.450.10.1

1cf3A2  

 

c.3.1.2

d1cf3a1 

 

d.16.1.1

d1cf3a2 

 

 

From the graphical match above, you can see that the signatures are grouped into three InterPro entries for Aspergillus niger glucose oxidase.  These entries give information about the domain architecture of the protein, as well as its family relationships.

To look at the family relationships, we need to consider entry IPR012132, which represents the alcohol oxidase family of proteins, and which has one signature: PIRSF000137 from the PIRSuperfamily database. 

The domain architecture of this glucose oxidase consists of two domains, an N-terminal FAD-binding domain and a C-terminal substrate-binding domain.  These domains have been classified by two InterPro entries.  IPR000172 represents the FAD-binding, GMC oxidoreductase N-terminal domain, and has three signatures: PF00732 from the PFAM database, and PS00623 and PS00624 from the PROSITE database.  This entry groups together different GMC oxidoreductase enzymes that share sequence similarity in their N-terminal domains.  IPR007867 represents the GMC oxidoreductase C-terminal domain, and has one signature: PF05199 from the PFAM database.  This entry groups together different GMC oxidoreductase enzymes that share sequence similarity in their C-terminal domains.

The remaining six entries in the table above give information on the structure of this protein, presenting known structural data from the structural database PDB (green stripe) and the structural classification databases CATH (pink stripe) and SCOP (black stripe) (the names such as 1cf3A1 are derived from the PDB entry upon which they are based, here PDB entry 1cf3, chain A, fragment 1).  The graphical match for the PDB entry 1cf3 displays the full length of the original PDB entry, here covering almost the entire protein.  The CATH and SCOP entries breakdown the PDB data into its constituent domains based on structure, and provide a structural classification for each domain.  SCOP divides the protein into two structural domains: the N-terminal FAD-binding domain is represented by d1cf3a1, which has a three-layer b/b/a sandwich structure and which is a discontiguous domain that includes the tip of the C-terminus of the protein; and the C-terminal (excluding the C-terminal tip) domain is represented by d1cf3a2, which has an a/b sandwich structure and which is inserted into the N-terminal domain.  CATH divides the protein into three discontiguous structural domains: domain 1, 1cf3A1, has a three-layer b/b/a sandwich structure; domain 2, 1cf3A2, has an irregular structure; and domain 3, 1cf3A3, has an a/b sandwich structure.

 

What the Structure Tells Us

 

            Structures associated with glucose oxidase can be viewed using AstexViewer®, which is linked from the Match Table via the logo  on the InterPro page (please note, there is no link directly from this page to the AstexViewer®, therefore you need to go to the  link on the InterPro page for P13006).  The AstexViewer® displays the PDB structure with the specific CATH or SCOP domain highlighted.

            There are structures available for glucose oxidase in the Protein Data Bank (PDB).  A detailed description and visualisation of the structural features of glucose oxidase and its importance to biosensors can be found at the PDB ‘Molecule of the Month’.  The crystallographic structures of glucose oxidase enzymes have provided insight into the mechanism of action of these important enzymes.

 

Next:   Table of Glucose Oxidase Enzymes

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