Difference between revisions of "Transformation of PGF2a to exPGF2a by PGT"

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(Transport Parameters)
(Transporter concentration)
 
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Line 17: Line 17:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
Line 26: Line 27:
 
pH: 7.5
 
pH: 7.5
 
Temp: 37 °C
 
Temp: 37 °C
 +
|2048
 
|<ref name="Kraft2010"> [https://www.ncbi.nlm.nih.gov/pubmed/20019365 M. Kraft ''The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost.'' Invest Ophthalmol Vis Sci. 2010 May;51(5):2504-11. doi: 10.1167/iovs.09-4290. Epub 2009 Dec 17.]</ref>
 
|<ref name="Kraft2010"> [https://www.ncbi.nlm.nih.gov/pubmed/20019365 M. Kraft ''The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost.'' Invest Ophthalmol Vis Sci. 2010 May;51(5):2504-11. doi: 10.1167/iovs.09-4290. Epub 2009 Dec 17.]</ref>
 
|-
 
|-
Line 34: Line 36:
 
pH: unknown
 
pH: unknown
 
Temp: 37 °C
 
Temp: 37 °C
 +
|512
 
|<ref name="Gose2016"> [https://www.ncbi.nlm.nih.gov/pubmed/26692285 Gose T. ''Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.'' Prostaglandins Other Lipid Mediat. 2016 Jan;122:10-7. doi: 10.1016/j.prostaglandins.2015.12.003. Epub 2015 Dec 10.]</ref>
 
|<ref name="Gose2016"> [https://www.ncbi.nlm.nih.gov/pubmed/26692285 Gose T. ''Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.'' Prostaglandins Other Lipid Mediat. 2016 Jan;122:10-7. doi: 10.1016/j.prostaglandins.2015.12.003. Epub 2015 Dec 10.]</ref>
 
|-
 
|-
Line 42: Line 45:
 
pH: unknown
 
pH: unknown
 
Temp: 37 °C
 
Temp: 37 °C
 +
|512
 
|<ref name="Gose2016"> [https://www.ncbi.nlm.nih.gov/pubmed/26692285 Gose T. ''Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.'' Prostaglandins Other Lipid Mediat. 2016 Jan;122:10-7. doi: 10.1016/j.prostaglandins.2015.12.003. Epub 2015 Dec 10.]</ref>
 
|<ref name="Gose2016"> [https://www.ncbi.nlm.nih.gov/pubmed/26692285 Gose T. ''Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.'' Prostaglandins Other Lipid Mediat. 2016 Jan;122:10-7. doi: 10.1016/j.prostaglandins.2015.12.003. Epub 2015 Dec 10.]</ref>
 
|-
 
|-
Line 50: Line 54:
 
pH: unknown
 
pH: unknown
 
Temp: unknown
 
Temp: unknown
 +
|192
 
|<ref name="Chi2010"> [http://www.sciencedirect.com/science/article/pii/S0006291X10005723 Chi Y. ''The prostaglandin transporter PGT transports PGH2'' Biochemical and Biophysical Research Communications, Volume 395, Issue 2, 30 April 2010, Pages 168–172]</ref>
 
|<ref name="Chi2010"> [http://www.sciencedirect.com/science/article/pii/S0006291X10005723 Chi Y. ''The prostaglandin transporter PGT transports PGH2'' Biochemical and Biophysical Research Communications, Volume 395, Issue 2, 30 April 2010, Pages 168–172]</ref>
 
|-
 
|-
Line 60: Line 65:
 
pH: 7
 
pH: 7
 
Temperature: 27
 
Temperature: 27
 +
|1024
 
|<ref name="Kanai1995"> [http://science.sciencemag.org/content/sci/268/5212/866.full.pdf Kanai N. ''Identification and Characterization of a
 
|<ref name="Kanai1995"> [http://science.sciencemag.org/content/sci/268/5212/866.full.pdf Kanai N. ''Identification and Characterization of a
 
Prostaglandin Transporter'' Science  12 May 1995:Vol. 268, Issue 5212, pp. 866-869, DOI: 10.1126/science.7754369]</ref>
 
Prostaglandin Transporter'' Science  12 May 1995:Vol. 268, Issue 5212, pp. 866-869, DOI: 10.1126/science.7754369]</ref>
Line 71: Line 77:
 
pH: 7
 
pH: 7
 
Temperature: 27
 
Temperature: 27
 +
|1024
 
|<ref name="Kanai1995"> [http://science.sciencemag.org/content/sci/268/5212/866.full.pdf Kanai N. ''Identification and Characterization of a
 
|<ref name="Kanai1995"> [http://science.sciencemag.org/content/sci/268/5212/866.full.pdf Kanai N. ''Identification and Characterization of a
 
Prostaglandin Transporter'' Science  12 May 1995:Vol. 268, Issue 5212, pp. 866-869, DOI: 10.1126/science.7754369]</ref>
 
Prostaglandin Transporter'' Science  12 May 1995:Vol. 268, Issue 5212, pp. 866-869, DOI: 10.1126/science.7754369]</ref>
Line 82: Line 89:
 
pH: 7
 
pH: 7
 
Temperature: 27
 
Temperature: 27
 +
|1024
 
|<ref name="Kanai1995"> [http://science.sciencemag.org/content/sci/268/5212/866.full.pdf Kanai N. ''Identification and Characterization of a
 
|<ref name="Kanai1995"> [http://science.sciencemag.org/content/sci/268/5212/866.full.pdf Kanai N. ''Identification and Characterization of a
 
Prostaglandin Transporter'' Science  12 May 1995:Vol. 268, Issue 5212, pp. 866-869, DOI: 10.1126/science.7754369]</ref>
 
Prostaglandin Transporter'' Science  12 May 1995:Vol. 268, Issue 5212, pp. 866-869, DOI: 10.1126/science.7754369]</ref>
Line 93: Line 101:
 
pH: 7
 
pH: 7
 
Temperature: 27
 
Temperature: 27
|<ref name="SHIGEKAZU1996"> [http://molpharm.aspetjournals.org/content/molpharm/50/4/736.full.pdf Shigekazu I. ''Structural Determinants of Substrates for the Prostaglandin Transporter PGT'' Molecular Pharmacology October 1996, 50 (4) 736-742; DOI: https://doi.org/10.1124/mol.50.4.736]</ref>
+
|1024
|-
 
|5.02E-05
 
|mM
 
|Human
 
|Substrate: PGF2a
 
Species: Human
 
Vector: HeLa Cell Line
 
pH: 7
 
Temperature: 27
 
|<ref name="SHIGEKAZU1996"> [http://molpharm.aspetjournals.org/content/molpharm/50/4/736.full.pdf Shigekazu I. ''Structural Determinants of Substrates for the Prostaglandin Transporter PGT'' Molecular Pharmacology October 1996, 50 (4) 736-742; DOI: https://doi.org/10.1124/mol.50.4.736]</ref>
 
|-
 
|0.005
 
|mM
 
|Human
 
|Substrate: 15-Keto-PGE2
 
Species: Human
 
Vector: HeLa Cell Line
 
pH: 7
 
Temperature: 27
 
|<ref name="SHIGEKAZU1996"> [http://molpharm.aspetjournals.org/content/molpharm/50/4/736.full.pdf Shigekazu I. ''Structural Determinants of Substrates for the Prostaglandin Transporter PGT'' Molecular Pharmacology October 1996, 50 (4) 736-742; DOI: https://doi.org/10.1124/mol.50.4.736]</ref>
 
|-
 
|0.005
 
|mM
 
|Human
 
|Substrate: 13,14-Dihydo-15-Keto-PGE2
 
Species: Human
 
Vector: HeLa Cell Line
 
pH: 7
 
Temperature: 27
 
|<ref name="SHIGEKAZU1996"> [http://molpharm.aspetjournals.org/content/molpharm/50/4/736.full.pdf Shigekazu I. ''Structural Determinants of Substrates for the Prostaglandin Transporter PGT'' Molecular Pharmacology October 1996, 50 (4) 736-742; DOI: https://doi.org/10.1124/mol.50.4.736]</ref>
 
|-
 
|3.82E-05
 
|mM
 
|Human
 
|Substrate: PGH2
 
Species: Human
 
Vector: HeLa Cell Line
 
pH: 7
 
Temperature: 27
 
 
|<ref name="SHIGEKAZU1996"> [http://molpharm.aspetjournals.org/content/molpharm/50/4/736.full.pdf Shigekazu I. ''Structural Determinants of Substrates for the Prostaglandin Transporter PGT'' Molecular Pharmacology October 1996, 50 (4) 736-742; DOI: https://doi.org/10.1124/mol.50.4.736]</ref>
 
|<ref name="SHIGEKAZU1996"> [http://molpharm.aspetjournals.org/content/molpharm/50/4/736.full.pdf Shigekazu I. ''Structural Determinants of Substrates for the Prostaglandin Transporter PGT'' Molecular Pharmacology October 1996, 50 (4) 736-742; DOI: https://doi.org/10.1124/mol.50.4.736]</ref>
 
|-
 
|-
Line 138: Line 107:
  
 
{| class="wikitable"
 
{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the PGT Kms distribution
 
! Mode (mM) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
 
! Mode (mM) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
 
|-
 
|-
Line 143: Line 113:
 
|}
 
|}
  
 
+
[[Image:133.jpg|none|thumb|500px|The estimated probability distribution for PGT 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>cat</sub>===
 
===k<sub>cat</sub>===
Line 154: Line 124:
 
! Transporter
 
! Transporter
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
Line 161: Line 132:
 
|Organism: Bacteria Escherichia coli
 
|Organism: Bacteria Escherichia coli
 
Back of the envelope calculation by BioNumbers: http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=102931
 
Back of the envelope calculation by BioNumbers: http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=102931
 +
|8
 
|<ref name="Waygood1980"> [https://www.ncbi.nlm.nih.gov/pubmed/6992959?dopt=Abstract Waygood EB ''Enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system of Escherichia coli. Purification to homogeneity and some properties.''Can J Biochem. 1980 Jan;58(1):40-8.]</ref>
 
|<ref name="Waygood1980"> [https://www.ncbi.nlm.nih.gov/pubmed/6992959?dopt=Abstract Waygood EB ''Enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system of Escherichia coli. Purification to homogeneity and some properties.''Can J Biochem. 1980 Jan;58(1):40-8.]</ref>
 
|-
 
|-
Line 168: Line 140:
 
|Organism: Bacteria Escherichia coli
 
|Organism: Bacteria Escherichia coli
 
Back of the envelop calculation on bionumbers http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=103159
 
Back of the envelop calculation on bionumbers http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=103159
 +
|8
 
|<ref name="Naftalin2007"> [https://www.ncbi.nlm.nih.gov/pubmed/17325012?dopt=Abstract Naftalin R. J. ''ELactose permease H+-lactose symporter: mechanical switch or Brownian ratchet?''Biophys J. 2007 May 15;92(10):3474-91. Epub 2007 Feb 26.]</ref>
 
|<ref name="Naftalin2007"> [https://www.ncbi.nlm.nih.gov/pubmed/17325012?dopt=Abstract Naftalin R. J. ''ELactose permease H+-lactose symporter: mechanical switch or Brownian ratchet?''Biophys J. 2007 May 15;92(10):3474-91. Epub 2007 Feb 26.]</ref>
 
|-
 
|-
Line 175: Line 148:
 
|Organism: Budding yeast Saccharomyces cerevisiae
 
|Organism: Budding yeast Saccharomyces cerevisiae
 
Back of the envelope calculation http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101737
 
Back of the envelope calculation http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101737
 +
|8
 
|<ref name="Ye2001"> [https://www.ncbi.nlm.nih.gov/pubmed/11561293?dopt=Abstract Ye L. ''Expression and activity of the Hxt7 high-affinity hexose transporter of Saccharomyces cerevisiae''Yeast. 2001 Sep 30;18(13):1257-67.]</ref>
 
|<ref name="Ye2001"> [https://www.ncbi.nlm.nih.gov/pubmed/11561293?dopt=Abstract Ye L. ''Expression and activity of the Hxt7 high-affinity hexose transporter of Saccharomyces cerevisiae''Yeast. 2001 Sep 30;18(13):1257-67.]</ref>
 
|-
 
|-
Line 180: Line 154:
  
 
{| class="wikitable"
 
{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the PGT kcat distribution
 
! Mode (min-1) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
 
! Mode (min-1) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
 
|-
 
|-
Line 185: Line 160:
 
|}
 
|}
  
 +
[[Image:132.jpg|none|thumb|500px|The estimated probability distribution for PGT 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.  ]]
  
 +
=== Transporter concentration ===
 +
 +
To convert the enzyme concentration from ppm to mM, the following [[Common equations#Enzyme concentration (mM)|equation]] was used.
  
=== Transporter concentration ===
 
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
 
|+  style="text-align: left;" | Abundance
 
|+  style="text-align: left;" | Abundance
Line 195: Line 173:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
Line 204: Line 183:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|2048
 
|<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>
 
|<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>
 
|-
 
|-
Line 213: Line 193:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
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>
 
|<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>
 
|-
 
|-
Line 222: Line 203:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|2048
 
|<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>
 
|<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>
 
|-
 
|-
Line 227: Line 209:
  
 
{| class="wikitable"
 
{| class="wikitable"
! Mode (mM) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
+
|+  style="text-align: left;" | Description of the PGT concentration distribution
 +
! Mode (ppm) !! Mode (mM) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
 
|-
 
|-
| 1.73E+01 || 4.72E+00 || 3.90E+00 || 1.02E+00
+
| 1.73E+01 ||9.57E-05|| 4.72E+00 || 3.90E+00 || 1.02E+00
 
|}
 
|}
 +
 +
[[Image:165.jpg|none|thumb|500px|The estimated probability distribution for PGT 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.  ]]
  
 
== References ==
 
== References ==
 
<references/>
 
<references/>

Latest revision as of 11:52, 30 May 2019

Return to overview

Prostaglandin Transporter


Rate equation

R101.PNG

Transport Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
0.0054 mM Human Eye Vector: HEK-OATP2A1 or HEK-OATP2B1 and the respective vector controls

Substrate: Latanoprost, a prostaglandin F2a analogue pH: 7.5 Temp: 37 °C

2048 [1]
0.000331 ± 0.000131 mM Transfected Human embryonic kidney cells (HEK293) Substrate: PGE2

pH: unknown Temp: 37 °C

512 [2]
0.007202 ± 0.000595 mM Transfected Human embryonic kidney cells (HEK293) Substrate: PGE3

pH: unknown Temp: 37 °C

512 [2]
0.000376 ± 3.4e-5 mM PGT-expressing Madin-Darby Canine Kidney Epithelial Cells (MDCK) cells Substrate: PGH2

pH: unknown Temp: unknown

192 [3]
9.40E-05 mM Human Substrate: PGE2

Species: Human Vector: HeLa Cell Line pH: 7 Temperature: 27

1024 [4]
0.000423 mM Human Substrate: TXB2

Species: Human Vector: HeLa Cell Line pH: 7 Temperature: 27

1024 [4]
0.007569 mM Human Substrate: 6-Keto-PGF1a

Species: Human Vector: HeLa Cell Line pH: 7 Temperature: 27

1024 [4]
4.87E-05 mM Human Substrate: PGE2

Species: Human Vector: HeLa Cell Line pH: 7 Temperature: 27

1024 [5]
Description of the PGT Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.10E-03 9.42E+01 -4.67E+00 1.45E+00
The estimated probability distribution for PGT 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.

kcat

No data available on the turnover of PGT/ an organic molecule transporter therefore based upon estimates made by http://book.bionumbers.org/what-are-the-rates-of-membrane-transporters/

Turnover Number
Value Units Transporter Notes Weight Reference
3.5 min-1 Glucose transporter ptsI Organism: Bacteria Escherichia coli

Back of the envelope calculation by BioNumbers: http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=102931

8 [6]
0.33 - 0.83 min-1 Rate of transport of H+/Lactose transporter Organism: Bacteria Escherichia coli

Back of the envelop calculation on bionumbers http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=103159

8 [7]
3.28 min-1 Catalytic Rate of transporter HXT7 Organism: Budding yeast Saccharomyces cerevisiae

Back of the envelope calculation http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101737

8 [8]
Description of the PGT kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.33E+00 7.30E+00 9.20E-01 8.00E-01
The estimated probability distribution for PGT 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.

Transporter concentration

To convert the enzyme concentration from ppm to mM, the following equation was used.

Abundance
Value Units Species Notes Weight Reference
125 ppm Human Vector:Lung

Enzyme: SLCO2A1 pH: 7.5 Temperature: 37 °C

2048 [9]
17.4 ppm Human Expression Vector: Esophagus

Enzyme: SLCO2A1 pH: 7.5 Temperature: 37 °C

2048 [10]
2.82 ppm Human Vector:Gut

Enzyme: SLCO2A1 pH: 7.5 Temperature: 37 °C

2048 [9]
Description of the PGT concentration distribution
Mode (ppm) Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.73E+01 9.57E-05 4.72E+00 3.90E+00 1.02E+00
The estimated probability distribution for PGT 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.

References

  1. M. Kraft The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol Vis Sci. 2010 May;51(5):2504-11. doi: 10.1167/iovs.09-4290. Epub 2009 Dec 17.
  2. 2.0 2.1 Gose T. Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3. Prostaglandins Other Lipid Mediat. 2016 Jan;122:10-7. doi: 10.1016/j.prostaglandins.2015.12.003. Epub 2015 Dec 10.
  3. Chi Y. The prostaglandin transporter PGT transports PGH2 Biochemical and Biophysical Research Communications, Volume 395, Issue 2, 30 April 2010, Pages 168–172
  4. 4.0 4.1 4.2 [http://science.sciencemag.org/content/sci/268/5212/866.full.pdf Kanai N. Identification and Characterization of a Prostaglandin Transporter Science 12 May 1995:Vol. 268, Issue 5212, pp. 866-869, DOI: 10.1126/science.7754369]
  5. Shigekazu I. Structural Determinants of Substrates for the Prostaglandin Transporter PGT Molecular Pharmacology October 1996, 50 (4) 736-742; DOI: https://doi.org/10.1124/mol.50.4.736
  6. Waygood EB Enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system of Escherichia coli. Purification to homogeneity and some properties.Can J Biochem. 1980 Jan;58(1):40-8.
  7. Naftalin R. J. ELactose permease H+-lactose symporter: mechanical switch or Brownian ratchet?Biophys J. 2007 May 15;92(10):3474-91. Epub 2007 Feb 26.
  8. Ye L. Expression and activity of the Hxt7 high-affinity hexose transporter of Saccharomyces cerevisiaeYeast. 2001 Sep 30;18(13):1257-67.
  9. 9.0 9.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  10. M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587