Difference between revisions of "Transformation of 15-Keto-PGE2 to 13,14-Dihydro-15-Keto-PGE2"

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NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different
 
NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different
 
concentrations of NADPH (0–60 mM)."
 
concentrations of NADPH (0–60 mM)."
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|512
 
| <ref name="Wu2008"> [https://www.ncbi.nlm.nih.gov/pubmed/19000823 "Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2", Structure. 2008 Nov 12;16(11):1714-23. doi: 10.1016/j.str.2008.09.007.]</ref>  
 
| <ref name="Wu2008"> [https://www.ncbi.nlm.nih.gov/pubmed/19000823 "Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2", Structure. 2008 Nov 12;16(11):1714-23. doi: 10.1016/j.str.2008.09.007.]</ref>  
 
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NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different
 
NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different
 
concentrations of NADPH (0–60 mM)."
 
concentrations of NADPH (0–60 mM)."
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|512
 
| <ref name="Wu2008"/>   
 
| <ref name="Wu2008"/>   
 
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Temperature:  37 ◦C
 
Temperature:  37 ◦C
 
Substrate: 15-Ketoprostaglandin E2
 
Substrate: 15-Ketoprostaglandin E2
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|  <ref name="Wu2008"/>   
 
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pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
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|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
|<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>
 
human proteome'' Nature, 2014 509, 582–587]</ref>
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pH: Unknown
 
pH: Unknown
 
Temperature: Unknown
 
Temperature: Unknown
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|Unknown
 
|Unknown
 
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pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
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|1024
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
|<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>
 
human proteome'' Nature, 2014 509, 582–587]</ref>
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Temperature: 298.15 K
 
Temperature: 298.15 K
 
Pressure: 1 bar
 
Pressure: 1 bar
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|<ref name="Silva2003”>[http://link.springer.com/article/10.1007/s00214-003-0476-9 P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345]</ref>
 
|<ref name="Silva2003”>[http://link.springer.com/article/10.1007/s00214-003-0476-9 P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345]</ref>
 
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Revision as of 16:01, 22 May 2019

Return to overview

PTGR-2 catalyses the reduction of the conjugated α,β-unsaturated double bond of 15-Keto-PGE2. This reaction is NADPH-dependant and generates 13,14-dihydro-15-keto-PGE2.

Reaction

Chemical equation

15-Keto-PGE2 + NAD(P)+ \rightleftharpoons 13,14-Dihydro-15-Keto-PGE2 + NAD(P)H

Rate equation

R69.PNG

Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
0.01121 ± 0.00014 mM Human Method: In vitro

Organism: Human Expression vector: E.coli Enzyme: PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: 15-Keto-PGE2

"For determining the KM and Vmax values for NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different concentrations of NADPH (0–60 mM)."

512 [1]
0.01587 ± 0.00171 mM Human Method: In vitro

Organism: Human Expression vector: E.coli Enzyme: e PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: NADPH

"For determining the KM and Vmax values for NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different concentrations of NADPH (0–60 mM)."

512 [1]
0.0496 ± 0.0058 mM Mouse Method: In vitro

Organism: Mouse Expression vector: Enzyme: 13,14-dehydro-15-oxoprostaglandin 13-reductase pH: 7.4 Temperature: 37 ◦C Substrate: 15-Ketoprostaglandin E2

[1]


Description of the PTGR-2 Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.20E-02 4.92E+00 -3.97E+00 6.71E-01
The estimated probability distribution for PTGR-2 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 PTGR-2 Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.19E-02 -3.97E+00 6.81E-01
The estimated probability distribution for PTGR-2 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

Note: Turnover values from EC 1.3.1.48 - 13,14-dehydro-15-oxoprostaglandin 13-reductase

Literature values
Value Units Species Notes Weight Reference
11.4 ± 0.9 min-1 Mouse Method: In vitro

Organism: Mouse Expression vector: Enzyme: 13,14-dehydro-15-oxoprostaglandin 13-reductase pH: 7.4 Temperature: 37 ◦C Substrate: 15-Ketoprostaglandin E2

384 [1]
Description of the PTGR-2 kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.14E+01 9.86E+00 3.22E+00 8.87E-01
The estimated probability distribution for PTGR-2 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 concentration

Literature values
Value Units Species Notes Weight Reference
162 ppm Human Expression Vector: Skin

Enzyme: PTGR2 pH: 7.5 Temperature: 37 °C

2048 [2]
80.9 ppm Human Expression Vector: Skin

Enzyme: PTGR2 pH: Unknown Temperature: Unknown

2048 Unknown
74.1 ppm Human Expression Vector: Oral Cavity

Enzyme: PTGR2 pH: 7.5 Temperature: 37 °C

1024 [2]
Description of the PTGR-2 concentration distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
8.65E+01 1.45E+00 4.58E+00 3.47E-01
The estimated probability distribution for PTGR-2 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 Units Species Notes Weight Reference
3.6006165 kcal/mol Unspecified Calculations with a Gaussian98 suite of programs

Enzyme: COX (Unspecific) Substrate: Arachidonate Temperature: 298.15 K Pressure: 1 bar

64 [3]
Description of the PTGR-2 Keq distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
2.28E-03 1.00E+01 -5.29E+00 8.91E-01
The estimated probability distribution for PTGR-2 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.

Misch

Half Life
Value Units Species Notes Reference
9.9 +/-0.2 minutes Dog In vivo

Temperature:37 pH:7

[4]
Vmax
Value Units Species Notes Reference
159.23 ± 0.71 nmol min-1 mg-1 Human Method: In vitro

Organism: Human Expression vector: E.coli Enzyme: PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: 15-Keto-PGE2

[1]
66.73 ± 1.36 nmol min-1 mg-1 Human Method: In vitro

Organism: Human Expression vector: E.coli Enzyme: PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: NADPH

[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2", Structure. 2008 Nov 12;16(11):1714-23. doi: 10.1016/j.str.2008.09.007. Cite error: Invalid <ref> tag; name "Wu2008" defined multiple times with different content Cite error: Invalid <ref> tag; name "Wu2008" defined multiple times with different content
  2. ↑ 2.0 2.1 [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]
  3. ↑ P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345
  4. ↑ W. Bothwell, "A radioimmunoassay for the unstable pulmonary metabolites of prostaglandin E1 and E2: an indirect index of their in vivo disposition and pharmacokinetics" Journal of Pharmacology and Experimental Therapeutics February 1982, 220 (2) 229-235
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