Inositol Monophosphatase: Difference between revisions
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=Inositol Monophosphatase (1DK4)= | =Inositol Monophosphatase (1DK4)= | ||
Inositol Monophosphatase is a homodimeric phosphatase. This protein structure is derived from the the methanogen ''Methanococcus jannaschii'' gene MJ0109. Curiously this protein shows both Inositol | {{STRUCTURE_1dk4|PDB=1dk4|SCENE=Sandbox_Reserved_326/Begininggood/1}} | ||
<scene name='Sandbox_Reserved_326/Begininggood/1'>Inositol Monophosphatase</scene> is a homodimeric phosphatase. This protein structure is derived from the the methanogen ''Methanococcus jannaschii'' gene MJ0109. Curiously this protein shows both Inositol Monophosphatase (IMPase) activity as well as Fructose-1,6-Bisphosphatase acivity (FBPase)<ref name="rasmol">PMID:11062561</ref>. This protein has a homolog in another archaeabacteria, such as [[1lbv|''Archaeoglobus fulgidus'']]<ref name="ref2">PMID:11940584</ref>. This Archaeal phosphatase is thought to be a precursor of many phophatases of higher organisms in Eukaryotes and Bacteria<ref name="rasmol"/>. | |||
__TOC__ | __TOC__ | ||
=''Methanococcus jannaschii'' | =[[Methanocaldococcus|''Methanococcus jannaschii'']]= | ||
''M. jannaschii'' are thermophilc methane producing | ''M. jannaschii'' are thermophilc methane producing archaeabacteria that were discovered in 1983 by the manned submersible ALVIN[http://www.springerlink.com/content/u8774k126821777x/]. They were sampled from the base of a deep sea hydrothermal vent in 2600m of water, local tempurature was 85°C. The complete 1.66 mega base pairs of its genome has been sequenced, about 1738 genes were identified. Most of them were determined to be homologous to eukaryotic proteins<ref>PMID: 8688087</ref>. | ||
=Structure= | =Structure= | ||
The general structure of this enzyme is a homodimer, composed of | 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 family<ref name="rasmol"/>. This particular structure has been crystalized in complex 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>) per subunit. Each subunit is composed of <scene name='Sandbox_Reserved_326/2nd_structure_unbcolour/2'>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. 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 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= | ||
IMPase activity within ''M. jannaschii'' is mainly limited to the production of a unique inositol, di-''myo''-inositol-1,1'-phosphate (DIP). Intracellular DIP concentrations increase usually in response to supraoptimal growth temperatures, and is involved in maintaining high cellular concentration of K+ which sustains optimal enzyme activity<ref>PMID: 9683472</ref>. | ===IMPase=== | ||
=== | IMPase activity within ''M. jannaschii'' is mainly limited to the production pathway of a unique inositol, di-''myo''-inositol-1,1'-phosphate (DIP), using DL-''myo''-inositol-1-phosphate as substrate. Intracellular DIP concentrations increase usually in response to supraoptimal growth temperatures, and is involved in maintaining high cellular concentration of K+ which sustains optimal enzyme activity<ref>PMID: 9683472</ref>. IMPase Km and Kcat at 85°C, 91±16μM and 4.2±0.2/s respectively<ref name="rasmol"/>. | ||
===FBPase=== | |||
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=== | |||
1DK4 is an extremely simple enzyme. As its 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"/>= | |||
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"/>. | |||
=References= | =References= | ||
<references/> | <references/> | ||
