Inositol Monophosphatase: Difference between revisions
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The general structure of this enzyme is a homodimer, composed of 252 amino acid residues per monomer. One subunit has a molecular mass of 28.6kDa. IMPase falls within the metallo-phosphatase super family<ref name="rasmol"/>. This particular structure has been crystalized in complex not with its actual ligand but with a <scene name='Sandbox_Reserved_326/Ligands/2'>phosphate group</scene> (<font color='red'>Red</font> and <font color='orange'>orange</font>), and three inhibitory Zn2+ ions (<font color='grey'>grey</font>) in the active site of each subunit. Additionally, each subunit possess its own large hydrophilic active site. Normally a Ca2+ ion is interacting with the active site, not shown here<ref name="ref2"/>. | The general structure of this enzyme is a homodimer, composed of 252 amino acid residues per monomer. One subunit has a molecular mass of 28.6kDa. IMPase falls within the metallo-phosphatase super family<ref name="rasmol"/>. This particular structure has been crystalized in complex not with its actual ligand but with a <scene name='Sandbox_Reserved_326/Ligands/2'>phosphate group</scene> (<font color='red'>Red</font> and <font color='orange'>orange</font>), and three inhibitory Zn2+ ions (<font color='grey'>grey</font>) in the active site of each subunit. Additionally, each subunit possess its own large hydrophilic active site. Normally a Ca2+ ion is interacting with the active site, not shown here<ref name="ref2"/>. | ||
One subunit of MJ0109 is composed of <scene name='Sandbox_Reserved_326/2nd_structure_unbcolour/3'>5 layers</scene> alternating <font color='green'>α helix</font>, <font color='gold'>β sheet</font>, to <font color='green'>α helix</font> from the N to C terminus. | |||
The active site is mostly conserved and is similar in sequence to [[1awb|Human IMPase]]. However, its overall tertiary structure is similar to a monomer of the ''Sus scrofa domesticus'', or [[1cnq|Pig, FBPase]]. | The active site is mostly conserved and is similar in sequence to [[1awb|Human IMPase]]. However, its overall tertiary structure is similar to a monomer of the ''Sus scrofa domesticus'', or [[1cnq|Pig, FBPase]]. | ||
=Function= | =Function= | ||
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Under normal conditions the MJ0109 gene product preferentially metabolizes the second last major step in [[gluconeogenesis]], fructose-1,6-bisphosphate substrate to fructose-6-phosphate. Relative to its IMPase activity, FBPase activity of MJ0109 is 1.63 times as active<ref name="rasmol"/>. This particular function was not immediately identified by genomic sequence alignment and was later determined using structual and kinetic analysis<ref name="rasmol"/>. FBPase Km and Kcat at 85°C, 38±9μM and 7.0±0.4/s respectively<ref name="rasmol"/>. | Under normal conditions the MJ0109 gene product preferentially metabolizes the second last major step in [[gluconeogenesis]], fructose-1,6-bisphosphate substrate to fructose-6-phosphate. Relative to its IMPase activity, FBPase activity of MJ0109 is 1.63 times as active<ref name="rasmol"/>. This particular function was not immediately identified by genomic sequence alignment and was later determined using structual and kinetic analysis<ref name="rasmol"/>. FBPase Km and Kcat at 85°C, 38±9μM and 7.0±0.4/s respectively<ref name="rasmol"/>. | ||
===Inhibitors=== | ===Inhibitors=== | ||
As the dual activity indicates, the substrate specificity of this enzyme is particularly low. Proposed evolutionary cousins of this enzyme are regulated by [[Adenosine monophosphate]] and [[Fructose 2,6-bisphosphate]]. However, there are no such allosteric regulatory binding sites on the MJ0109 protein. Additionally, ''M. jannaschii'' IMPase has a [[IC50]] for Li+ of >150mM, compared to the Li+ IC50 of human IMPase <1mM<ref name="rasmol"/>. | |||
=Evolution<ref name="rasmol"/>= | =Evolution<ref name="rasmol"/>= | ||
It is generally well received that [[hyperthermophile|hyperthermophiles]] are near the oldest phyletic group, with a very slow rate of evolution<ref name="rasmol"/>. This is due to the rather unforgiving environment toward mutations of these microbes. Given that the MJ0109 protein lacks substrate specificity and regulatory sites, and possess activity of two separate pathways in Eukaryotes; it is a reasonable assumption that this enzyme is an evolutionary "snap shot" of an original phosphatase<ref name="rasmol"/>. | It is generally well received that [[hyperthermophile|hyperthermophiles]] are near the oldest phyletic group, with a very slow rate of evolution<ref name="rasmol"/>. This is due to the rather unforgiving environment toward mutations of these microbes. Given that the MJ0109 protein lacks substrate specificity and regulatory sites, and possess activity of two separate pathways in Eukaryotes; it is a reasonable assumption that this enzyme is an evolutionary "snap shot" of an original phosphatase approximation<ref name="rasmol"/>. | ||
=References= | =References= | ||
<references/> | <references/> | ||
