Difference between revisions of "Transformation of PGH2 to PGD2"

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[[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> FA \rightleftharpoons AA </math></center>
+
<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;" | Michaelis-Menten Constants
+
|+  style="text-align: left;" | Literature values
 
|-
 
|-
 
! Value
 
! Value
Line 18: Line 23:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
−
|4.00E-03
+
|0.0138
 
|<math> mM </math>
 
|<math> mM </math>
 
|Human  
 
|Human  
−
|Cerebrospinal Fluid
+
|Expression Vector: Human Cell
−
|<ref name="Watanabe1994"> [http://www.ncbi.nlm.nih.gov/pubmed/20667974 Watanabe K. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules.'' Biochem Biophys Res Commun. 1994 Sep 15;203(2):1110-6.]</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
−
|Human Wild Type Enzyme
+
|Expression Vector: Cerebrospinal Fluid
−
|<ref name="Zhou2010"> [http://www.ncbi.nlm.nih.gov/pubmed/8093029 Zhou Y. , "Identification of beta-trace as prostaglandin D synthase.'' FASEB J. 2010 Dec;24(12):4668-77. doi: 10.1096/fj.10-164863. Epub 2010 Jul 28.]</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;" | Enzyme Turnover Numbers
+
|+  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
−
| Wild type (Paper includes 13 mutants of the enzyme)
+
|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;" | Enzyme Concentrations
+
|+  style="text-align: left;" | Literature values
 
|-
 
|-
 
! Value
 
! Value
Line 58: Line 144:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
−
|0.000256
+
|156
−
|mM
+
|<math> ppm </math>
−
|Human
+
|Human
−
|20 ug/3ml of a 26 kDa protein. Cerebral Fluid.
+
|Expression Vector: Pancreas
−
|<ref name="Watanabe1994"> [http://www.ncbi.nlm.nih.gov/pubmed/20667974 Watanabe K. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules.'' Biochem Biophys Res Commun. 1994 Sep 15;203(2):1110-6.]</ref>
+
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>
 
|-
 
|-
−
|0.769
+
|5.72
−
|mM
+
|kcal/mol
−
|Human
+
|Not stated
−
|20mg/ml of 26 kDa protein
+
|Estimated
−
|<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>  
+
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

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

R21 PGH2 - PGD2.jpg

Chemical equation

PGH2 \rightleftharpoons PGD2

Rate equation

R21.PNG

Enzyme Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
0.0138 mM Human Expression Vector: Human Cell

Enzyme: PGDS pH: 8 Temperature: 25

512 [1]
4.00E-03 mM Human Expression Vector: Cerebrospinal Fluid

Enzyme: PGDS pH:10 Temperature: Unspecified

256 [2]
0.50 mM Human Expression Vector: E. Coli.

Enzyme: PGDS pH:6.5 Temperature: Unspecified

128 [3]
1.40E-02 mM Rat Expression Vector: Cerebrospinal Fluid

Enzyme: PGDS pH:7 Temperature: 25

256 [4]
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
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.

Kmp

Description of the PGDS Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.30E-02 -4.02E+00 5.69E-01
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.


kcat

Literature values
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]
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
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 equation was used.

Literature values
Value Units Species Notes Weight Reference
156 ppm Human Expression Vector: Pancreas

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

1024 [7]
101 ppm Human Expression Vector: Oral Cavity

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

1024 [8]
67.9 ppm Human Expression Vector: Esophagus

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

1024 [7]
44.5 ppm Human Expression Vector:Skin

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

2048 [8]
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
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.

Keq

Literature values
Gibbs Free Energy Change Units Species Notes Weight Reference
caption kJ/mol 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]
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
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

  1. ↑ 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.
  2. ↑ Watanabe K. , "Identification of beta-trace as prostaglandin D synthase."Biochem Biophys Res Commun. 1994 Sep 15;203(2):1110-6.
  3. ↑ 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.
  4. ↑ Urade Y. , "Purification and characterization of rat brain prostaglandin D synthetase." J Biol Chem. 1985 Oct 15;260(23):12410-5.
  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.
  6. ↑ [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. ↑ 7.0 7.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  8. ↑ 8.0 8.1 M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  9. ↑ [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]
  10. ↑ 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

Related Reactions

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