Inositol Monophosphatase

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Inositol monophosphatase dimer complex with Zn+2 (grey) and phosphate ions, 1dk4

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1 Introduction
2 Methanococcus jannaschii
3 Structure
4 Function
5 Evolution
6 3D Structures of Inositol Monophosphatase

Introduction

(1dk4) 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)^[1]. This protein has a homolog in other archaeabacteria, such as Archaeoglobus fulgidus^[2]. This Archaeal phosphatase is thought to be a precursor of many phophatases of higher organisms in Eukaryotes and Bacteria^[1].

Methanococcus jannaschii

M. jannaschii are thermophilc methane producing archaeabacteria that were discovered in 1983 by the manned submersible ALVIN[1]. 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^[3].

Structure

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^[1]. This particular structure has been crystalized in complex not with its actual ligand but with a (Red and orange), and three inhibitory Zn²⁺ ions (grey) 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^[2].

One subunit of MJ0109 is composed of alternating α helix, β sheet, to α helix from the N to C terminus.

The active site is mostly conserved and is similar in sequence to Human IMPase. However, its overall tertiary structure is similar to a monomer of the Sus scrofa domesticus, FBPase (Fructose-1,6-bisphosphatase).

Function

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^[4]. IMPase K_m and K_cat at 85°C; 91±16μM and 4.2±0.2/s, respectively^[1].

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, the FBPase activity of MJ0109 is 1.63 times as active^[1]. This particular function was not immediately identified by genomic sequence alignment and was later determined using structual and kinetic analysis^[1]. FBPase K_m and K_cat at 85°C; 38±9μM and 7.0±0.4/s, respectively^[1].

FBPase/IMPase

An unusual phosphatase found in several hyperthermophilic organisms which has dual activity toward inositol monophosphate and fructose 1,6-bisphosphate^[5].

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^[1].

Evolution

It is generally well received that hyperthermophiles are near the oldest phyletic group, with a very slow rate of evolution^[1]. 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^[1].

3D Structures of Inositol Monophosphatase

Inositol monophosphatase 3D structures

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 ^1.8 ^1.9 Stec B, Yang H, Johnson KA, Chen L, Roberts MF. MJ0109 is an enzyme that is both an inositol monophosphatase and the 'missing' archaeal fructose-1,6-bisphosphatase. Nat Struct Biol. 2000 Nov;7(11):1046-50. PMID:11062561 doi:10.1038/80968
↑ ^2.0 ^2.1 Stieglitz KA, Johnson KA, Yang H, Roberts MF, Seaton BA, Head JF, Stec B. Crystal structure of a dual activity IMPase/FBPase (AF2372) from Archaeoglobus fulgidus. The story of a mobile loop. J Biol Chem. 2002 Jun 21;277(25):22863-74. Epub 2002 Apr 8. PMID:11940584 doi:http://dx.doi.org/10.1074/jbc.M201042200
↑ Bult CJ, White O, Olsen GJ, Zhou L, Fleischmann RD, Sutton GG, Blake JA, FitzGerald LM, Clayton RA, Gocayne JD, Kerlavage AR, Dougherty BA, Tomb JF, Adams MD, Reich CI, Overbeek R, Kirkness EF, Weinstock KG, Merrick JM, Glodek A, Scott JL, Geoghagen NS, Venter JC. Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science. 1996 Aug 23;273(5278):1058-73. PMID:8688087
↑ Chen L, Spiliotis ET, Roberts MF. Biosynthesis of Di-myo-inositol-1,1'-phosphate, a novel osmolyte in hyperthermophilic archaea. J Bacteriol. 1998 Aug;180(15):3785-92. PMID:9683472
↑ Stieglitz KA, Johnson KA, Yang H, Roberts MF, Seaton BA, Head JF, Stec B. Crystal structure of a dual activity IMPase/FBPase (AF2372) from Archaeoglobus fulgidus. The story of a mobile loop. J Biol Chem. 2002 Jun 21;277(25):22863-74. Epub 2002 Apr 8. PMID:11940584 doi:http://dx.doi.org/10.1074/jbc.M201042200

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Kadagn Klepsch, OCA, Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Inositol_Monophosphatase"

Category: Topic Page

@@ Line 1: / Line 1: @@
-<!-- PLEASE DO NOT DELETE THIS TEMPLATE -->
+<StructureSection load='1dk4' size='340' side='right' caption='Inositol monophosphatase dimer complex with Zn+2 (grey) and phosphate ions, [[1dk4]]' scene='Sandbox_Reserved_326/Begininggood/1'>
-{{Template:Sandbox_Reserved_BCMB307}}
- <!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
+=Introduction=
-=Inositol Monophosphatase (1DK4)=
+<scene name='Sandbox_Reserved_326/Begininggood/1'>Inositol Monophosphatase</scene> ([[1dk4]]) 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 other 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"/>.
-{{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__
 =''Methanococcus jannaschii''=
-[[Methanocaldococcus|''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>.
+[http://en.wikipedia.org/wiki/Methanocaldococcus|''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=
-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 Zn<sup>2+</sup> 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 Ca<sup>2+</sup> ion is interacting with the active site, not shown here<ref name="ref2"/>.
-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.
+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'', [[1cnq|FBPase]] ([[Fructose-1,6-bisphosphatase]]).
 =Function=
 ===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"/>.
+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 K<sub>m</sub> and K<sub>cat</sub> 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"/>.
+Under normal conditions the MJ0109 gene product preferentially metabolizes the second last major step in [http://en.wikipedia.org/wiki/Gluconeogenesis| gluconeogenesis], fructose-1,6-bisphosphate substrate to fructose-6-phosphate. Relative to its IMPase activity, the 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 K<sub>m</sub> and K<sub>cat</sub> at 85°C; 38±9μM and 7.0±0.4/s, respectively<ref name="rasmol"/>.
+===FBPase/IMPase===
+An unusual phosphatase found in several hyperthermophilic organisms which has dual activity toward inositol monophosphate and fructose 1,6-bisphosphate<ref>PMID:11940584</ref>.
 ===Inhibitors===
-DK4 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"/>.
+As the dual activity indicates, the substrate specificity of this enzyme is particularly low. Proposed evolutionary cousins of this enzyme are regulated by [http://en.wikipedia.org/wiki/Adenosine_monophosphate| Adenosine monophosphate] and [http://en.wikipedia.org/wiki/Fructose_2,6-bisphosphate| Fructose 2,6-bisphosphate]. However, there are no such allosteric regulatory binding sites on the MJ0109 protein.  Additionally, ''M. jannaschii'' IMPase has a [http://en.wikipedia.org/wiki/IC50| IC50] for Li+ of >150mM, compared to the Li+ IC50 of human IMPase <1mM<ref name="rasmol"/>.
-=Evolution<ref name="rasmol"/>=
+=Evolution=
-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 [http://en.wikipedia.org/wiki/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"/>.
+=3D Structures of Inositol Monophosphatase=
+[[Inositol monophosphatase 3D structures]]
+</StructureSection>
 =References=
 <references/>
+[[Category:Topic Page]]