Role of Tryptophan Hydroxylase Phe313 in Determining Substrate Specificity

2002 ◽  
Vol 292 (3) ◽  
pp. 639-641 ◽  
Author(s):  
S.Colette Daubner ◽  
Graham R. Moran ◽  
Paul F. Fitzpatrick
Keyword(s):  
Substrate Specificity ◽  
Tryptophan Hydroxylase

Conformation of the Substrate and Pterin Cofactor Bound to Human Tryptophan Hydroxylase. Important Role of Phe313 in Substrate Specificity†

Biochemistry ◽  
2001 ◽  
Vol 40 (51) ◽  
pp. 15591-15601 ◽  
Author(s):  
Jeffrey McKinney ◽  
Knut Teigen ◽  
Nils Åge Frøystein ◽  
Clotilde Salaün ◽  
Per M. Knappskog ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Tryptophan Hydroxylase ◽  
Pterin Cofactor

Possible role of a histidine residue in the substrate specificity of yeast d-aspartate oxidase

2015 ◽  
pp. mvv108 ◽  
Author(s):  
Shouji Takahashi ◽  
Kozue Shimada ◽  
Shunsuke Nozawa ◽  
Masaru Goto ◽  
Katsumasa Abe ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Histidine Residue

scholarly journals ROLE OF THE ALLELIC VARIATION IN THE 5-HYDROXYTRYPTAMINE RECEPTOR 1A (HTR1A) AND THE TRYPTOPHAN HYDROXYLASE 2 (TPH2) GENES IN THE DEVELOPMENT OF PTSD

2019 ◽  
Vol 31 (2) ◽  
pp. 256-262 ◽  
Author(s):  
Aferdita Goci Uka ◽  
◽  
Ferid Agani ◽  
Afrim Blyta ◽  
Blerina Hoxha ◽  
...  
Keyword(s):  
Tryptophan Hydroxylase ◽  
Allelic Variation ◽  
Tryptophan Hydroxylase 2

Time- and age-dependent effects of serotonin on gasping and autoresuscitation in neonatal mice

2013 ◽  
Vol 114 (12) ◽  
pp. 1668-1676 ◽  
Author(s):  
Jianping Chen ◽  
Jennifer Magnusson ◽  
Gerard Karsenty ◽  
Kevin J. Cummings
Keyword(s):  
Heart Rate ◽  
Tryptophan Hydroxylase ◽  
Single Injection ◽  
Heart Rate Recovery ◽  
Wild Type ◽  
Tryptophan Hydroxylase 2 ◽  
Age Dependent ◽  
Long Time ◽  
Time Required

The role of brain stem serotonin (5-hydroxytryptamine, 5-HT) in autoresuscitation in neonatal life is unclear. We hypothesized that a specific loss of 5-HT would compromise gasping and autoresuscitation mainly in the second postnatal week and that acute restoration of 5-HT would reverse the defects. We exposed postnatal day (P)4–5, P8–9, and P11–12 tryptophan-hydroxylase-2 knockout ( TPH2−/−) and wild-type littermates (WT) to 10 episodes of anoxia (97% N2, 3% CO2), measuring survival, gasp latency, gasp frequency ( fB), and the time required to restore eupnea and heart rate. We also tested P8–9 TPH2−/− mice after restoring 5-HT with a single injection of 5-hydroxytryptophan (5-HTP) 1–2 h before testing or with multiple injections beginning 24 h before testing. At P4–5 and P8–9, but not at P11–12, gasp latency and the recovery of eupnea were delayed ∼2- to 3-fold in TPH2−/− pups compared with WT ( P < 0.001). At all ages, TPH2−/− pups displayed reduced gasp fB (∼20–30%; P < 0.001) and delayed heart rate recovery (∼60%; P = 0.002) compared with WT littermates. TPH2−/− survival was reduced compared with WT ( P < 0.001), especially at P8–9 and P11–12 ( P = 0.004). Whereas 1–2 h of 5-HTP treatment improved the gasp latency and fB of P8–9 TPH2−/− pups, improved cardiorespiratory recovery and survival required 24 h of treatment. Our data suggest that 5-HT operates over a long time span (∼24 h) to improve survival during episodic severe hypoxia. Early in development (P4–9), 5-HT is critical for both respiratory and cardiovascular components of autoresuscitation; later (P11–12), it is critical mainly for cardiovascular components. Nevertheless, the effect of 5-HT deficiency on survival is most striking from P8 to P12.

scholarly journals Molecular Basis of Substrate Recognition of Endonuclease Q from the Euryarchaeon Pyrococcus furiosus

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Miyako Shiraishi ◽  
Shigenori Iwai
Keyword(s):  
Dna Repair ◽  
Bacillus Subtilis ◽  
Substrate Specificity ◽  
Molecular Basis ◽  
Pyrococcus Furiosus ◽  
Substrate Recognition ◽  
Base Flipping ◽  
Content Type ◽  
Cleavage Activity

ABSTRACT Endonuclease Q (EndoQ), a DNA repair endonuclease, was originally identified in the hyperthermophilic euryarchaeon Pyrococcus furiosus in 2015. EndoQ initiates DNA repair by generating a nick on DNA strands containing deaminated bases and an abasic site. Although EndoQ is thought to be important for maintaining genome integrity in certain bacteria and archaea, the underlying mechanism catalyzed by EndoQ remains unclear. Here, we provide insights into the molecular basis of substrate recognition by EndoQ from P. furiosus (PfuEndoQ) using biochemical approaches. Our results of the substrate specificity range and the kinetic properties of PfuEndoQ demonstrate that PfuEndoQ prefers the imide structure in nucleobases along with the discovery of its cleavage activity toward 5,6-dihydrouracil, 5-hydroxyuracil, 5-hydroxycytosine, and uridine in DNA. The combined results for EndoQ substrate binding and cleavage activity analyses indicated that PfuEndoQ flips the target base from the DNA duplex, and the cleavage activity is highly dependent on spontaneous base flipping of the target base. Furthermore, we find that PfuEndoQ has a relatively relaxed substrate specificity; therefore, the role of EndoQ in restriction modification systems was explored. The activity of the EndoQ homolog from Bacillus subtilis was found not to be inhibited by the uracil glycosylase inhibitor from B. subtilis bacteriophage PBS1, whose genome is completely replaced by uracil instead of thymine. Our findings suggest that EndoQ not only has additional functions in DNA repair but also could act as an antiviral enzyme in organisms with EndoQ. IMPORTANCE Endonuclease Q (EndoQ) is a lesion-specific DNA repair enzyme present in certain bacteria and archaea. To date, it remains unclear how EndoQ recognizes damaged bases. Understanding the mechanism of substrate recognition by EndoQ is important to grasp genome maintenance systems in organisms with EndoQ. Here, we find that EndoQ from the euryarchaeon Pyrococcus furiosus recognizes the imide structure in nucleobases by base flipping, and the cleavage activity is enhanced by the base pair instability of the target base, along with the discovery of its cleavage activity toward 5,6-dihydrouracil, 5-hydroxyuracil, 5-hydroxycytosine, and uridine in DNA. Furthermore, a potential role of EndoQ in Bacillus subtilis as an antiviral enzyme by digesting viral genome is demonstrated.

The Role of the 5'-Hydroxyl Group of Adenosine in Determining Substrate Specificity for Adenosine Deaminase

1967 ◽  
Vol 10 (5) ◽  
pp. 908-912 ◽  
Author(s):  
Alexander. Bloch ◽  
Morris J. Robins ◽  
James R. McCarthy
Keyword(s):  
Substrate Specificity ◽  
Adenosine Deaminase ◽  
Hydroxyl Group

scholarly journals The role of the Cys191-Cys220 disulfide bond in trypsin: new targets for engineering substrate specificity

1997 ◽  
Vol 10 (4) ◽  
pp. 405-411 ◽  
Author(s):  
E. C. Wang ◽  
S. H. Hung ◽  
M. Cahoon ◽  
L. Hedstrom
Keyword(s):  
Substrate Specificity ◽  
Disulfide Bond ◽  
New Targets
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