scholarly journals On the Role of Short and Strong Hydrogen Bonds on the Mechanism of Action of a Model Chymotrypsine Active Site

2009 ◽  
Vol 113 (19) ◽  
pp. 5769-5772 ◽  
Author(s):  
German Miño ◽  
Renato Contreras
Keyword(s):  
Hydrogen Bonds ◽  
Mechanism Of Action ◽  
Active Site

Investigations into the role of sulfhydryl groups in the mechanism of action of the nitrates

1982 ◽  
Vol 60 (10) ◽  
pp. 1261-1266 ◽  
Author(s):  
J. A. Moffat ◽  
P. W. Armstrong ◽  
G. S. Marks
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Mechanism Of Action ◽  
Active Site ◽  
Sulfhydryl Reagents ◽  
Response Curves ◽  
Sh Groups ◽  
Nitrobenzoic Acid ◽  
Sh Group

The mechanism by which nitroglycerin (GTN) initiates relaxation in vascular smooth muscle is not known. According to one hypothesis a specific nitrate receptor exists with a key sulfhydryl (SH) group in the active site. The current study was performed with sulfhydryl reagents in helical strips of the canine medial saphenous vein from 20 dogs to examine the role of the SH group in the action of GTN. The reagents used were 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) and p-chloromercuribenzoate (PCMB) which bind to and inactivate SH groups, and dithiothreitol (DTT), an SH reducing agent. It was anticipated that DTNB and PCMB would decrease the sensitivity to GTN while DTT might increase the sensitivity to GTN. Treatment of strips with PCMB and DTNB did not alter the dose–response curves for GTN. In contrast, following DTT treatment (1 × 10−4 M) the maximum response to GTN (10−5 M) was significantly reduced from 80.3% ± 4.0 (SD) in control strips to 46.9% ± 4.4 (SD) in the treated strips. These data suggest that relaxation induced by GTN in vascular smooth muscle occurs by a mechanism other than interaction with membrane SH groups.

scholarly journals An analysis of the role of active site protic residues of cytochrome P-450s: mechanistic and mutational studies on 17α-hydroxylase-17,20-lyase (P-45017α also CYP17)

1998 ◽  
Vol 330 (2) ◽  
pp. 967-974 ◽  
Author(s):  
Peter LEE-ROBICHAUD ◽  
E. Monika AKHTAR ◽  
Muhammad AKHTAR
Keyword(s):  
Hydrogen Bonds ◽  
Active Site ◽  
Catalytic Properties ◽  
Active Form ◽  
Proton Donor ◽  
Wild Type ◽  
Cleavage Reaction ◽  
Acyl Carbon ◽  
Hydroxylation Reaction

Certain cytochrome P-450s involved in the transformation of steroids catalyse not only the hydroxylation process associated with the group of enzymes, but also an acyl-carbon cleavage reaction. The hydroxylation occurs using an iron-monooxygen species while the acyl-carbon cleavage has been suggested to be promoted by an iron peroxide. In this paper we have studied the role of active site protic residues, Glu305 and Thr306, in modulating the two activities. For this purpose, the kinetic parameters for the hydroxylation reaction (pregnenolone → 17α-hydroxypregnenolone) and two different versions of acyl-carbon cleavage (17α-hydroxypregnenolone → dehydroepiandrosterone and 3β-hydroxyandrost-5-ene-17β-carbaldehyde → 3β-hydroxyandrost-5,16-diene+androst-5-ene-3β,17α-diol) were determined using the wild-type human CYP17 and its eight different single and double mutants. In addition the propensity of the proteins to undergo a subtle rearrangement converting the 450 nm active-form into an inactive counterpart absorbing at 420 nm, was monitored by measuring the of the P-450 → P-420 conversion. The results are interpreted to draw the following conclusions. The functional groups of Glu305 and Thr306 do not directly participate in the two proton delivery steps required for hydroxylation but may be important participants for the provision of a net work of hydrogen bonds for ‘activating’ water that then acts as a proton donor. The loss of any one of these residues is, therefore, only partially debilitating. That the mutation of Thr306 impairs the hydroxylation reaction more than it does the acyl-carbon cleavage is consistent with the detailed mechanistic scheme considered in this paper. Furthermore attention is drawn to the fact that the mutation of Glu305 and Thr306 subtly perturbed the architecture of the active site, which affects the geometry of this region of the protein and therefore its catalytic properties.

SOME ASPECTS OF THE FUNCTION OF FSH- AND LH-LIKE HORMONES IN NORMAL AND HYPOPHYSECTOMIZED FEMALE RATS, IN CONNECTION WITH RESERPINE ADMINISTRATION

1965 ◽  
Vol 49 (1) ◽  
pp. 28-38
Author(s):  
M. Grönroos ◽  
E. Mäkinen ◽  
K. Lahtinen ◽  
R. Tirri
Keyword(s):  
Mechanism Of Action ◽  
Biological Effect ◽  
Female Rats ◽  
Histological Picture ◽  
Peripheral Effect ◽  
Pituitary Secretion

ABSTRACT The effect of reserpine on the secretion of FSH and LH was studied as well as the role of the peripheral effect of reserpine after hypophysectomy. The results in the unoperated animals suggest that reserpine inhibits the pituitary secretion of both FSH and LH. Both these hormones combined with reserpine had a very different biological effect than was seen without reserpine. HCG (LH-like) and particularly PMS (FSH-like) hormones combined with reserpine caused definite enlargement of the ovaries. In the hypophysectomized groups, the effect of the PMS and HCG hormones administered together with reserpine or without it was the same with regard to the weight of the ovaries, but not with regard to their histological picture. On the basis of these results, reserpine may be said to have a peripheral effect although the nature of its mechanism of action is difficult to state. Reserpine probably affects the ovaries by inhibiting the follicular cycle and, consequently, the formation of new and more mature follicles.

Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

2019 ◽  
Vol 18 (8) ◽  
pp. 581-597 ◽  
Author(s):  
Ambreen Fatima ◽  
Yasir Hasan Siddique
Keyword(s):  
Medicinal Plants ◽  
Mechanism Of Action ◽  
Neurodegenerative Disorders ◽  
Treatment Strategies ◽  
Dietary Supplementation ◽  
Plant Polyphenols ◽  
Promising Candidate ◽  
Naturally Occurring ◽  
The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

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