Enzymes of Glycolysis

What InterPro tells us: phase I enzymes

Below are examples from InterPro for the enzymes at each step in the first phase of glycolysis, and their family relationships with other proteins. As you can see from below, the enzymes do not share sequence or structural homology with one another, and are therefore found in different protein families.

P19367 Human hexokinase I entry from InterPro

Interpro Entry	Method accession	Graphical match	Method name
IPR001312	PD001109		Hexokinase
IPR001312	PF00349		Hexokinase_1
IPR001312	PF03727		Hexokinase_2
IPR001312	PR00475		HEXOKINASE
IPR001312	PS00378		HEXOKINASES
Classification	Domain ID	Structural Domains
3.30.420.40.1	1czaN1
3.30.420.40.1	1hkbA3
3.40.367.20.1	1dgkN4
3.40.367.20.1	1czaN2
c.55.1.3	d1qhaa1
c.55.1.3	d1hkba4
c.55.1.3	d1czan3
c.55.1.3	d1czan2

Mammalian hexokinases I-III are structurally similar, consisting of a duplication of the two-domain yeast-type hexokinases (mammalian hexokinase IV (glucokinase) is similar to the yeast enzymes). Both the N- and C-terminal halves bind glucose and glucose-6-phosphate, though in types I and III, only the C-terminal half supports catalysis (both support catalysis in type II). Each half has one large and one small domain.

The example in the graphical match above is of hexokinase I, which is represented by a single InterPro entry, IPR001312, the hexokinase family of proteins. There are five signatures in IPR001312: PD001109 from PRODOM database, which covers the entire protein sequence, PF00349 and PF03727 from the PFAM database, which represent the four domains as two pairs of similar sequences, PR00475 from the PRINTS database, which uses motifs from conserved regions spanning the full sequence, and PS00378 from the PROSITE database, which uses a highly conserved region involved in substrate binding.

The remaining eight entries in the table are from the structural classification databases CATH (1czaN1, 1hkbA3, 1dgkN4, 1czaN2) and SCOP (d1qhaa1, d1hkba4, d1czan3, d1czan2); the names such as d1qhaa1 are derived from the PDB entry upon which they are based, here PDB entry 1qha, chain A region 1. If you follow the links to these databases, you will find descriptions of the structural features and classification of these domains, as well as links to the corresponding PDB entries. The structural databases show small extra regions associated with each domain, as can be seen above. This is due to a structural definition of the domain, as opposed to the definition based on sequence seen with the PFAM signatures.

P06744 Human phosphoglucose isomerase entry from InterPro

Interpro Entry	Method accession	Graphical match	Method name
IPR001672	PF00342		PGI
IPR001672	PR00662		G6PISOMERASE
IPR001672	PS00174		P_GLUCOSE_ISOMERASE_2
IPR001672	PS00765		P_GLUCOSE_ISOMERASE_1
Classification	Domain ID	Structural Domains
3.40.50.1890.2	1iatA2
c.80.1.2	d1iria_

Phosphoglucose isomerase is a two-domain protein with two protruding loops, the smaller domain is inserted within the larger domain. The top part of the large domain together with one of the protruding loops might participate in inducing the neurotrophic activity.

From the second graphical match, you can see that the signatures in InterPro for phosphoglucose isomerase (PGI) fall into a single entry, IPR001672, the PGI family of proteins. The four signatures in this entry are: PF00342 from the PFAM database, which covers nearly the entire sequence, PR00662 from the PRINTS database, which uses motifs drawn from short conserved regions in the central and C-terminal portions of the alignment, and PS00174 and PS00765 from the PROSITE database, which use two highly conserved regions of the protein.

The remaining two entries in the table are from the structural classification databases CATH (1iatA2) and SCOP (d1iria_), which supply descriptions of the structural features and classification of this protein, and links to the corresponding PDB entries. The CATH entry describes the smaller PGI domain that is inserted within the larger domain, while the SCOP entry describes the entire protein.

P06998 E. coli phosphofructokinase entry from InterPro

Interpro Entry	Method accession	Graphical match	Method name
IPR000023	PD000707		Ppfruckinase
IPR000023	PF00365		PFK
IPR000023	PR00476		PHFRCTKINASE
IPR000023	PS00433		PHOSPHOFRUCTOKINASE
Classification	Domain ID	Structural Domains
3.40.50.450.1	1pfkA1
3.40.50.460.1	1pfkA2
c.89.1.1	d1pfka_

The phosphofructokinase (PFK) monomer consists of two domains, one involved in ATP binding and the other containing both the substrate-binding site and the allosteric site.

From the third graphical match, you can see that the signatures in InterPro for PFK fall into a single entry, IPR000023, which represents the PFK family of proteins. The eukaryotic proteins are also represented by IPR009161, which is a child of IPR000023 that represents eukaryotic-type PFK. There are four signatures in the IPR000023 entry: PD000707 from the PRODOM database, PF00365 from the PFAM database, both of which cover all but the C-terminal portion of the protein, PR00476 from the PRINTS database, which uses motifs drawn from short conserved regions spanning the full alignment, and PS00433 from the PROSITE database, which uses a region containing three basic residues involved in substrate-binding.

The remaining three entries in the table are from the structural classification databases CATH (1pfkA1 and 1pfkA2) and SCOP (d1pfka_). The CATH entry describes each of the two PFK domains, while the SCOP entry describes the entire protein.

P04075 Human fructose-bisphosphate aldolase A entry from InterPro

Interpro Entry	Method accession	Graphical match	Method name
IPR000741	PD001128		Aldolase_I
IPR000741	PF00274		Glycolytic
IPR000741	PS00158		ALDOLASE_CLASS_I
Classification	Domain ID	Structural Domains
3.20.20.70.2	1ald00
c.1.10.1	d1ald__

From the fourth graphical match, you can see that the signatures in InterPro for fructose-bisphosphate aldolase (FBPA) fall into a single entry, IPR000741, which represents the FBPA, class I (eukaryotic) family of proteins. There are three signatures in this entry: PD001128 from the PRODOM database, PF00274 from the PFAM database, both of which describe the entire protein sequence, and PS00158 from the PROSITE database, which uses the region surrounding a highly conserved lysine involved in the Schiff-base.

The remaining two entries in the table are from the structural classification databases CATH (1ald00) and SCOP (d1ald__), both of which are derived from the same PDB entry (1ald) describing the entire protein.

P04790 Escherichia coli triosephosphate isomerase entry from InterPro

Interpro Entry	Method accession	Graphical match	Method name
IPR000652	PD001005		Triophos_ismrse
IPR000652	PF00121		TIM
IPR000652	PS00171		TIM
IPR000652	SSF51351		Triophos_ismrse
IPR000652	TIGR00419		tim
Classification	Domain ID	Structural Domains
3.20.20.90.1	1tmhA0
c.1.1.1	d1tmha_

From the fifth graphical match, you can see that the signatures in InterPro for triosephosphate isomerase (TPI) fall into a single entry, IPR000652, which represents the TPI family of proteins. There are five signatures in this entry: PD001005 from the PRODOM database, PF00121 from the PFAM database, SSF51351 from the SUPERFAMILY database, TIGR00419 from the TIGRFAM database, all of which represent the entire sequence of this single domain protein, and PS00171, which uses sequence around the active site glutamic acid residue.

The remaining two entries in the table are from the structural databases CATH (1tmhA0) and SCOP (d1tmha_), both of which are derived from the same PDB entry (1tmh) describing the entry protein.

Next: What InterPro tells us: phase II enzymes

Previous: Phase II: the enzymes in detail