Difference between revisions of "Transformation of PGH2 to PGD2"
(→Parameters) |
|||
(22 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
[[Welcome to the In-Silico Model of Cutaneous Lipids Wiki | Return to overview]] | [[Welcome to the In-Silico Model of Cutaneous Lipids Wiki | Return to overview]] | ||
+ | |||
+ | The isomerisation of PGH2 to PGD2 can be performed by prostaglandin D synthase (PGDS) and prostaglandin F synthase (PGFS). PGDS yields a hydroxyl group at C9 and a ketone group at C11. Two isoforms of PGDS have been found in humans, the lipocalin isoform, L-PGDS, does not require glutathione for catalysis whereas the hemopoietic type, H-PGDS, does require glutathione. | ||
+ | |||
== Reaction == | == Reaction == | ||
[[File:R21_PGH2_-_PGD2.jpg|center|500px]] | [[File:R21_PGH2_-_PGD2.jpg|center|500px]] | ||
Line 5: | Line 8: | ||
==Chemical equation== | ==Chemical equation== | ||
− | <center><math> | + | <center><math> PGH2 \rightleftharpoons PGD2 </math></center> |
== Rate equation == | == Rate equation == | ||
+ | [[File:R21.PNG|center|500px]] | ||
− | == Parameters == | + | == Enzyme Parameters == |
+ | ===K<sub>ms</sub>=== | ||
{|class="wikitable sortable" | {|class="wikitable sortable" | ||
− | |+ style="text-align: left;" | | + | |+ style="text-align: left;" | Literature values |
|- | |- | ||
! Value | ! Value | ||
Line 18: | Line 23: | ||
! Species | ! Species | ||
! Notes | ! Notes | ||
+ | ! Weight | ||
! Reference | ! Reference | ||
|- | |- | ||
− | | | + | |0.0138 |
|<math> mM </math> | |<math> mM </math> | ||
|Human | |Human | ||
− | | | + | |Expression Vector: Human Cell |
− | |<ref | + | Enzyme: PGDS |
+ | pH: 8 | ||
+ | Temperature: 25 | ||
+ | |512 | ||
+ | |<ref>[http://www.ncbi.nlm.nih.gov/pubmed/20667974 Zhou Y. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules." FASEB J. 2010 Dec;24(12):4668-77. doi: 10.1096/fj.10-164863. Epub 2010 Jul 28.]</ref> | ||
|- | |- | ||
|4.00E-03 | |4.00E-03 | ||
|<math> mM </math> | |<math> mM </math> | ||
|Human | |Human | ||
− | | | + | |Expression Vector: Cerebrospinal Fluid |
− | |<ref | + | Enzyme: PGDS |
+ | pH:10 | ||
+ | Temperature: Unspecified | ||
+ | |256 | ||
+ | |<ref>[http://www.ncbi.nlm.nih.gov/pubmed/8093029 Watanabe K. , "Identification of beta-trace as prostaglandin D synthase."Biochem Biophys Res Commun. 1994 Sep 15;203(2):1110-6. ]</ref> | ||
+ | |- | ||
+ | |0.50 | ||
+ | |<math> mM </math> | ||
+ | |Human | ||
+ | |Expression Vector: E. Coli. | ||
+ | Enzyme: PGDS | ||
+ | pH:6.5 | ||
+ | Temperature: Unspecified | ||
+ | |128 | ||
+ | |<ref>[https://www.ncbi.nlm.nih.gov/pubmed/10871602 Pinzar E , "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis." J Biol Chem. 2000 Oct 6;275(40):31239-44. ]</ref> | ||
+ | |- | ||
+ | |1.40E-02 | ||
+ | |<math> mM </math> | ||
+ | |Rat | ||
+ | |Expression Vector: Cerebrospinal Fluid | ||
+ | Enzyme: PGDS | ||
+ | pH:7 | ||
+ | Temperature: 25 | ||
+ | |256 | ||
+ | |<ref>[https://www.ncbi.nlm.nih.gov/pubmed/3930495 Urade Y. , "Purification and characterization of rat brain prostaglandin D synthetase." J Biol Chem. 1985 Oct 15;260(23):12410-5.]</ref> | ||
|- | |- | ||
+ | |} | ||
+ | {| class="wikitable" | ||
+ | |+ style="text-align: left;" | Description of the PGDS Kms distribution | ||
+ | ! Mode (mM) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ) | ||
+ | |- | ||
+ | | 1.35E-02 || 3.78E+00 || -3.44E+00 || 9.29E-01 | ||
+ | |} | ||
+ | |||
+ | [[Image:65.jpg|none|thumb|500px|The estimated probability distribution for PGDS Kms. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale. ]] | ||
+ | |||
+ | ===K<sub>mp</sub>=== | ||
+ | {| class="wikitable" | ||
+ | |+ style="text-align: left;" | Description of the PGDS Kmp distribution | ||
+ | ! Mode (mM) !! Location parameter (µ) !! Scale parameter (σ) | ||
+ | |- | ||
+ | | 1.30E-02 || -4.02E+00 || 5.69E-01 | ||
|} | |} | ||
+ | |||
+ | [[Image:66.jpg|none|thumb|500px|The estimated probability distribution for PGDS Kmp. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale. ]] | ||
+ | |||
+ | |||
+ | ===k<sub>cat</sub>=== | ||
{|class="wikitable sortable" | {|class="wikitable sortable" | ||
− | |+ style="text-align: left;" | | + | |+ style="text-align: left;" | Literature values |
|- | |- | ||
! Value | ! Value | ||
Line 42: | Line 97: | ||
! Species | ! Species | ||
! Notes | ! Notes | ||
+ | ! Weight | ||
! Reference | ! Reference | ||
|- | |- | ||
Line 47: | Line 103: | ||
| per minute | | per minute | ||
| Human | | Human | ||
− | | | + | |Expression Vector: Human Cell |
+ | Enzyme: PGDS | ||
+ | pH: 8 | ||
+ | Temperature: 25 | ||
+ | |256 | ||
| <ref name="Zhou2010"> [http://www.ncbi.nlm.nih.gov/pubmed/20667974 Zhou Y. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules.'' FASEB J. 2010 Dec;24(12):4668-77.]</ref> | | <ref name="Zhou2010"> [http://www.ncbi.nlm.nih.gov/pubmed/20667974 Zhou Y. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules.'' FASEB J. 2010 Dec;24(12):4668-77.]</ref> | ||
+ | |- | ||
+ | |1302 | ||
+ | | per minute | ||
+ | |Human | ||
+ | |Expression Vector: E. Coli. | ||
+ | Enzyme: PGDS | ||
+ | pH:6.5 | ||
+ | Temperature: Unspecified | ||
+ | |128 | ||
+ | |<ref name="Pinzar2000"> [https://www.ncbi.nlm.nih.gov/pubmed/10871602 Pinzar E , "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis.'' | ||
+ | J Biol Chem. 2000 Oct 6;275(40):31239-44. ]</ref> | ||
+ | |- | ||
+ | |} | ||
+ | |||
+ | {| class="wikitable" | ||
+ | |+ style="text-align: left;" | Description of the PGDS kcat distribution | ||
+ | ! Mode (min-1) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ) | ||
+ | |- | ||
+ | | 1.58E+02 || 1.50E+00 || 5.10E+00 || 2.00E-01 | ||
|} | |} | ||
+ | |||
+ | [[Image:67.jpg|none|thumb|500px|The estimated probability distribution for PGDS kcat. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale. ]] | ||
+ | |||
+ | |||
+ | === Enzyme concentrations === | ||
+ | |||
+ | To convert the enzyme concentration from ppm to mM, the following [[Common equations#Enzyme concentration (mM)|equation]] was used. | ||
{|class="wikitable sortable" | {|class="wikitable sortable" | ||
− | |+ style="text-align: left;" | | + | |+ style="text-align: left;" | Literature values |
|- | |- | ||
! Value | ! Value | ||
Line 58: | Line 144: | ||
! Species | ! Species | ||
! Notes | ! Notes | ||
+ | ! Weight | ||
! Reference | ! Reference | ||
|- | |- | ||
− | | | + | |156 |
− | | | + | |<math> ppm </math> |
− | |Human | + | |Human |
− | | | + | |Expression Vector: Pancreas |
− | |<ref name=" | + | Enzyme: PGDS |
+ | pH: 7.5 | ||
+ | Temperature: 37 °C | ||
+ | |1024 | ||
+ | |<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref> | ||
+ | |- | ||
+ | |101 | ||
+ | |<math> ppm </math> | ||
+ | |Human | ||
+ | |Expression Vector: Oral Cavity | ||
+ | Enzyme: PGDS | ||
+ | pH: 7.5 | ||
+ | Temperature: 37 °C | ||
+ | |1024 | ||
+ | |<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the human proteome'' Nature, 2014 509, 582–587]</ref> | ||
+ | |- | ||
+ | |67.9 | ||
+ | |<math> ppm </math> | ||
+ | |Human | ||
+ | |Expression Vector: Esophagus | ||
+ | Enzyme: PGDS | ||
+ | pH: 7.5 | ||
+ | Temperature: 37 °C | ||
+ | |1024 | ||
+ | |<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref> | ||
+ | |- | ||
+ | |44.5 | ||
+ | |<math> ppm </math> | ||
+ | |Human | ||
+ | |Expression Vector:Skin | ||
+ | Enzyme: PGDS | ||
+ | pH: 7.5 | ||
+ | Temperature: 37 °C | ||
+ | |2048 | ||
+ | |<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the human proteome'' Nature, 2014 509, 582–587]</ref> | ||
+ | |- | ||
+ | |} | ||
+ | |||
+ | {| class="wikitable" | ||
+ | |+ style="text-align: left;" | Description of the PGDS concentration distribution | ||
+ | ! Mode (ppm) !! Mode (mM) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ) | ||
+ | |- | ||
+ | | 6.76E+01 ||3.74E-04|| 1.64E+00 || 4.41E+00 || 4.49E-01 | ||
+ | |} | ||
+ | |||
+ | [[Image:161.jpg|none|thumb|500px|The estimated probability distribution for PGDS concentration. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale. ]] | ||
+ | |||
+ | ===K<sub>eq</sub>=== | ||
+ | {|class="wikitable sortable" | ||
+ | |+ style="text-align: left;" | Literature values | ||
+ | |- | ||
+ | ! Gibbs Free Energy Change | ||
+ | ! Units | ||
+ | ! Species | ||
+ | ! Notes | ||
+ | ! Weight | ||
+ | ! Reference | ||
+ | |- | ||
+ | |[[File:Kume2014.png|options|caption]] | ||
+ | |<math> kJ/mol </math> | ||
+ | |Human | ||
+ | |Expression Vector: E. Coli | ||
+ | Enzyme: L-PGDS | ||
+ | pH: 8 | ||
+ | Temperature: 25 | ||
+ | |64 | ||
+ | |<ref name="Kume2014"> [http://ac.els-cdn.com/S0014579314000982/1-s2.0-S0014579314000982-main.pdf?_tid=7f323a24-6543-11e6-82ac-00000aab0f01&acdnat=1471525305_289e200c1e492c5fa693179a5396fd82 Kume S., "Fine-tuned broad binding capability of human lipocalin-type prostaglandin D synthase for various small lipophilic ligands'' FEBS Letters | ||
+ | Volume 588, Issue 6, 18 March 2014, Pages 962–969]</ref> | ||
|- | |- | ||
− | | | + | |5.72 |
− | | | + | |kcal/mol |
− | | | + | |Not stated |
− | | | + | |Estimated |
− | |<ref name=" | + | Enzyme: PGDS |
+ | Substrate: Arachidonate | ||
+ | Product: PGD2 | ||
+ | pH: 7.3 | ||
+ | ionic strength: 0.25 | ||
+ | |64 | ||
+ | |<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=PROSTAGLANDIN-D-SYNTHASE-RXN Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471]</ref> | ||
+ | |} | ||
+ | |||
+ | {| class="wikitable" | ||
+ | |+ style="text-align: left;" | Description of the PGDS Keq distribution | ||
+ | ! Mode !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ) | ||
|- | |- | ||
+ | | 7.46E+04 || 1.00E+01 || 1.20E+01 || 8.90E-01 | ||
|} | |} | ||
+ | |||
+ | [[Image:68.jpg|none|thumb|500px|The estimated probability distribution for PGDS Keq. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale. ]] | ||
== References == | == References == |
Latest revision as of 07:51, 21 August 2019
The isomerisation of PGH2 to PGD2 can be performed by prostaglandin D synthase (PGDS) and prostaglandin F synthase (PGFS). PGDS yields a hydroxyl group at C9 and a ketone group at C11. Two isoforms of PGDS have been found in humans, the lipocalin isoform, L-PGDS, does not require glutathione for catalysis whereas the hemopoietic type, H-PGDS, does require glutathione.
Contents
Reaction
Chemical equation
Rate equation
Enzyme Parameters
Kms
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
0.0138 | Human | Expression Vector: Human Cell
Enzyme: PGDS pH: 8 Temperature: 25 |
512 | [1] | |
4.00E-03 | Human | Expression Vector: Cerebrospinal Fluid
Enzyme: PGDS pH:10 Temperature: Unspecified |
256 | [2] | |
0.50 | Human | Expression Vector: E. Coli.
Enzyme: PGDS pH:6.5 Temperature: Unspecified |
128 | [3] | |
1.40E-02 | Rat | Expression Vector: Cerebrospinal Fluid
Enzyme: PGDS pH:7 Temperature: 25 |
256 | [4] |
Mode (mM) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
1.35E-02 | 3.78E+00 | -3.44E+00 | 9.29E-01 |
Kmp
Mode (mM) | Location parameter (µ) | Scale parameter (σ) |
---|---|---|
1.30E-02 | -4.02E+00 | 5.69E-01 |
kcat
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
158.4 | per minute | Human | Expression Vector: Human Cell
Enzyme: PGDS pH: 8 Temperature: 25 |
256 | [5] |
1302 | per minute | Human | Expression Vector: E. Coli.
Enzyme: PGDS pH:6.5 Temperature: Unspecified |
128 | [6] |
Mode (min-1) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
1.58E+02 | 1.50E+00 | 5.10E+00 | 2.00E-01 |
Enzyme concentrations
To convert the enzyme concentration from ppm to mM, the following equation was used.
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
156 | Human | Expression Vector: Pancreas
Enzyme: PGDS pH: 7.5 Temperature: 37 °C |
1024 | [7] | |
101 | Human | Expression Vector: Oral Cavity
Enzyme: PGDS pH: 7.5 Temperature: 37 °C |
1024 | [8] | |
67.9 | Human | Expression Vector: Esophagus
Enzyme: PGDS pH: 7.5 Temperature: 37 °C |
1024 | [7] | |
44.5 | Human | Expression Vector:Skin
Enzyme: PGDS pH: 7.5 Temperature: 37 °C |
2048 | [8] |
Mode (ppm) | Mode (mM) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|---|
6.76E+01 | 3.74E-04 | 1.64E+00 | 4.41E+00 | 4.49E-01 |
Keq
Gibbs Free Energy Change | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
Human | Expression Vector: E. Coli
Enzyme: L-PGDS pH: 8 Temperature: 25 |
64 | [9] | ||
5.72 | kcal/mol | Not stated | Estimated
Enzyme: PGDS Substrate: Arachidonate Product: PGD2 pH: 7.3 ionic strength: 0.25 |
64 | [10] |
Mode | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
7.46E+04 | 1.00E+01 | 1.20E+01 | 8.90E-01 |
References
- ↑ Zhou Y. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules." FASEB J. 2010 Dec;24(12):4668-77. doi: 10.1096/fj.10-164863. Epub 2010 Jul 28.
- ↑ Watanabe K. , "Identification of beta-trace as prostaglandin D synthase."Biochem Biophys Res Commun. 1994 Sep 15;203(2):1110-6.
- ↑ Pinzar E , "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis." J Biol Chem. 2000 Oct 6;275(40):31239-44.
- ↑ Urade Y. , "Purification and characterization of rat brain prostaglandin D synthetase." J Biol Chem. 1985 Oct 15;260(23):12410-5.
- ↑ Zhou Y. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules. FASEB J. 2010 Dec;24(12):4668-77.
- ↑ [https://www.ncbi.nlm.nih.gov/pubmed/10871602 Pinzar E , "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis. J Biol Chem. 2000 Oct 6;275(40):31239-44. ]
- ↑ 7.0 7.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
- ↑ 8.0 8.1 M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
- ↑ [http://ac.els-cdn.com/S0014579314000982/1-s2.0-S0014579314000982-main.pdf?_tid=7f323a24-6543-11e6-82ac-00000aab0f01&acdnat=1471525305_289e200c1e492c5fa693179a5396fd82 Kume S., "Fine-tuned broad binding capability of human lipocalin-type prostaglandin D synthase for various small lipophilic ligands FEBS Letters Volume 588, Issue 6, 18 March 2014, Pages 962–969]
- ↑ Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471