Autoactivator

An enzyme in which the single catalytic residue is at the N-terminus of the protein. Many Ntn-hydrolases are synthesized as precursors and autoactivate the precursors are therefore peptidases, even if the mature enzyme has no further proteolytic activity. Three of the beta subunits of the proteasome are Ntn-hydrolases. 

The various interactions of the constituents required for the formation of bradykinin are shown in figure 2. The initiating step is a slow autoactivation of factor XII [10]. However, once this has occurred and prekallikrein is converted to kallikrein, there is... 

Factor Xlla converts prekallikrein to kallikrein and kallikrein cleaves HK to generate bradykinin. There is also an important positive feedback in the system in which the kallikrein generated rapidly converts unactivated factor XII to activated factor XII, and the rate of this reaction is hundreds of times faster than the rate of autoactivation [11]. Therefore, much of the unactivated factor XII can be cleaved and activated by kallikrein. Cl inhibitor inhibits all functions of factor Xlla and it is one of two major plasma kallikrein inhibitors. Thus all functions of kallikrein are also inhibited, including the feedback activation of factor XII, the cleavage of HK, and the activation of plasma pro-urokinase [66] to lead to plasmin formation. Cl inhibitor also inhibits the fibrinolytic enzyme plasmin, although it is a relatively minor inhibitor compared to a2-antiplasmin or a2-macroglobulin. 

Silverberg M, Dunn J, Garen L, Kaplan A Autoactivation of human Hageman factor. Demonstration utilizing a synthetic substrate. J Biol Chem 1980 255 7281-7286. 

Tankersley DL, Finlayson JS Kinetics of activation and autoactivation of human factor XII. Biochemistry 1984 23 273-279. 

Mineral dust-induced ROMs contributes to pulmonary fibrosis, malignancy, hypersensitivity and emphysema (Doelman etctl., 1990 Kamp etui., 1992). The involvement of ROMs in pulmonary fibrotic reactions is indicated by the participation of PMN oxidants in the autoactivation of latent coUagenase (Weiss et al., 1985). Prolyl hydroxylase, a key enzyme in collagen fibril formation, has been shown to be dependent on the reaction of superoxide with prolyl residues (Myllyla et al., 1979). 

Weiss, S.J., Peppin, G., Ortiz, X., Ragsdale, C. and Test, S.T. (1985). Oxidative autoactivation of latent collagenase by human neutrophils. Science 227, 747-749. 

The activity of factor Vila is enhanced astronomically (10 millionfold) upon binding to tissue factor. The VII or VHa-tissue factor complex activates factors IX and X and autoactivates factor VII. Although the activity of the tissue factor-factor VII complex is expressed without the presence of the negatively charged phosphatidylserine, the activity can be enhanced by its presence (9). 

Another important requirement for the chosen bait protein is that it should not yield autoactivation of transcription factor activity. This may occur in the GAL4 and LexA systems if the bait actually is a transcription factor or if the bait mimics the transcription factor activity. Autoactivation is evident if the DNA-BD bait construct is cotransformed into competent yeast with an empty AD vector and the resultant transformants show reporter gene enzyme activities and growth on SD media. Obviously, this needs to be avoided because cDNA library screening with such a bait will result in the detection of many false positives. 

Autoactivation may be circumvented by modification of the bait protein usually by the construction of truncation or deletion bait proteins that do not yield autoactivation. The disadvantage is that this may result in the loss of protein-protein interaction domains. Again, the use of two different yeast two-hybrid systems in parallel would negate these potential problems. O Figure 19-4 shows an example of manipulation... 

Boyle et al. (2001) used the Ciphergen SELDI protein chip to analyze the secretion and autoactivation of a cysteine protease (SpeB) from Streptococcus pyogenes that has been implicated in the onset of group A streptococcal infections and may contribute to toxic shock symptoms. SpeB could be detected at 0.75 ng protein in a 30-min assay based upon SELDI-TOF... 

Fig. 2. Activation mechanism of caspases. Receptors convey activating signals to adapters that facilitate oligomerization and subsequent autoactivation of long prodomain caspases (I). Caspases transactivate other procaspases upon activation (11).

Autophosphorylation of receptor tyrosine kinases has a double effect The tyrosine kinase activity undergoes autoactivation by phosphorylation of Tyr residues localized in or close to the active center (see 8.1.3). In addition, Tyr residues that lie outside the active center are phosphorylated. The phosphotyrosine residues thereby created serve as binding sites for effector molecules next in the sequence of the signal transduction pathway (see Fig. 8.6). 

The fact that the visual imagery of my dream is synthetic and bizarre could itself be isomorphic to the autoactivation of the visual brain—to the near simultaneous activation of visual networks encoding general barn features, features of my particular barn, and the local architectural elements, cement and stone, that I was playing with on my walk last night. 

Activation-synthesis model. (A) Systems model. (B) Wiring diagram. As a result of disinhibition caused by cessation of aminergic neuronal firing, brainstem reticular systems autoactivate. Their outputs have effects including depolarization of afferent terminals causing phasic presynaptic inhibition and blockade of external stimuli, especially during the bursts of REM, and postsynaptic hyperpolarization... 

Zymogens of cysteine proteases usually have a long terminal extension which is removed, sometimes by autoactivation. Propapain has a 107-residue extension.343 The 322-residue cathepsin B carries an unusually short 62-residue extension in its proenzyme form.315 343 344 In every case the N-terminal extension folds into a domain, one of whose functions is to block the active site cleft. 

N-Terminal nucleophile hydrolases autoactivation of 621 Termites, protozoa in 19 Tertiary structure of a protein 59 TES buffer 99... 

Collins, P.R., Stack, C.M., O Neill, S.M., Doyle, S., Ryan, T., Brennan, G.P., Mousley, A., Stewart, M., Maule, A.G., Dalton, J.P. and Donnelly, S. (2004) Cathepsin L1, the major protease involved in liver fluke (Fasciola hepatica) virulence propeptide cleavage sites and autoactivation of the zymogen secreted from gastrodermal cells. Journal of Biological Chemistry 279, 1 7038-1 7046. 

Mikolajczyk SD, Millar LS, Marker KM, et al. Ala217 is important for the catalytic function and autoactivation of prostate-specific human kallikrein 2. Eur J Biochem 1997 246 440 146. 

Ekins S, Ring BJ, Binkley SN, Hall SD, Wrighton SA (1998a) Autoactivation and activation of cytochrome P450s. Int J Clin Pharmacol Ther 36, 642-651. 

Lin, L., Sohar, I., Lackland, H., and Lobel, P. (2001). The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH., J. 

Kmi would be the standard Michaelis constant for the binding of the first substrate, if [ESS] = 0. Km2 would be the standard Michaelis constant for the binding of the second substrate, if [E] = 0 (i.e., the first binding site is saturated). In the complete equation, these constants are not true Km values, but their form (i.e., Km] = (k2 + k25)/k 2) and significance are analogous. Likewise, k25 and k35 are Vmi/Et and Vm2/Et terms when the enzyme is saturated with one and two substrate molecules, respectively. Equation (10) describes several non-Michaelis-Menten kinetic profiles. Autoactivation (sigmoidal saturation curve) occurs when k35 > k24 or Km2 < Km 1, substrate inhibition occurs when k24 > 35, and a biphasic saturation... 

The DISC-induced procaspase assembly results in the autoactivation of caspases 8 and 10. The DISC process of caspase activation seems to be analogous to the apoptosome process of caspase 9 activation. Caspase 8, in turn, cleaves and activates caspase 3, which is responsible for the apoptotic signal amplification with subsequent cell collapse. 

Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES (1998), Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization, Mol. Cell 1 949-957. 

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