Enzyme redesign and interactions of substrate analogues with sterol methyltransferase to understand phytosterol diversity, reaction mechanism and the nature of the active site

2005 ◽  
Vol 33 (5) ◽  
pp. 1189-1196 ◽  
Author(s):  
W.D. Nes
Keyword(s):  
Active Site ◽  
Functional Divergence ◽  
Product Distribution ◽  
Site Directed Mutagenesis ◽  
Site Model ◽  
Bifunctional Enzymes ◽  
And Function ◽  
The Relationship ◽  
Sterol Methyltransferase

Several STM (sterol methyltransferase) genes have been cloned, sequenced and expressed in bacteria recently, making it possible to address questions of the relationship between sterol structure and function. The active site and mechanism of action of a set of phylogenetically diverse SMTs have been probed by site-directed mutagenesis as well as by using substrate and related analogues of the SMT-catalysed reaction. An active-site model has been developed that is in accord with the results presented, which is consistent with the hypothesis that SMTs are bifunctional enzymes kinetically responsible to bind Δ24-acceptor sterols of specific steric and electronic character and rigid orientation imposed by multiple hydrophobic active site contacts exacted from a common waxy core. Functional divergence influenced by the architectural role of sterols in membranes is considered to govern the evolution of product distribution and specificity of individual SMTs as discussed.

Characterization of anEscherichia coliSulfite Oxidase Homologue Reveals the Role of a Conserved Active Site Cysteine in Assembly and Function†

Biochemistry ◽  
2005 ◽  
Vol 44 (30) ◽  
pp. 10339-10348 ◽  
Author(s):  
Stephen J. Brokx ◽  
Richard A. Rothery ◽  
Guijin Zhang ◽  
Derek P. Ng ◽  
Joel H. Weiner
Keyword(s):  
Active Site ◽  
Active Site Cysteine ◽  
And Function

An exploration of adolescent nonsuicidal self-injury and religious coping

2014 ◽  
Vol 26 (3) ◽  
pp. 345-349 ◽  
Author(s):  
Nicholas J. Westers ◽  
Mark Rehfuss ◽  
Lynn Olson ◽  
Constance M. Wiemann
Keyword(s):  
Religious Coping ◽  
Self Injury ◽  
Negative Religious Coping ◽  
Religious Constructs ◽  
And Function ◽  
Role Of Religion ◽  
The Relationship ◽  
Pearson Correlations ◽  
Nonsuicidal Self Injury

Abstract Many adolescents who engage in nonsuicidal self-injury (NSSI) self-identify as religious, but the role of religion in their NSSI is not known. This exploratory study examined the relationship between religious coping and religiousness among adolescents who self-injure and the function of their NSSI. Thirty adolescents aged 12–19 years who had engaged in NSSI participated in an interview and completed questionnaires. Multiple regressions were used to examine the relationship between religious coping and NSSI, and Pearson correlations were used to assess the relationship between religiousness and function of NSSI. Greater use of positive religious coping was associated with lower likelihood of engaging in NSSI to rid oneself of unwanted emotions, whereas greater use of negative religious coping was associated with greater likelihood of engaging in NSSI for this reason as well as to avoid punishment or unwanted responsibility. Higher religiousness was associated with greater use of NSSI to communicate with or gain attention from others, whereas lower religiousness was associated with greater use of NSSI to relieve unwanted emotions. Having a greater understanding of how religious constructs are related to the various functions served by NSSI may inform treatment of this population, particularly among religious youth who self-injure.

scholarly journals The Relationship between Personal Resources and Depression in a Sample of Victims of Cyberbullying: Comparison of Groups with and without Symptoms of Depression

2020 ◽  
Vol 17 (24) ◽  
pp. 9307
Author(s):  
Lourdes Rey ◽  
Cirenia Quintana-Orts ◽  
Sergio Mérida-López ◽  
Natalio Extremera
Keyword(s):  
Mental Health ◽  
Emotional Intelligence ◽  
Depressive Symptoms ◽  
Clinical Symptoms ◽  
Personal Resources ◽  
Symptoms Of Depression ◽  
And Function ◽  
The Relationship ◽  
Adolescent Victims

Previous research has highlighted the relationship between being cybervictimised and the presence of clinical symptoms, such as depression. To date, however, there has been no comparative analysis of the personal resources profiles of adolescent victims of cyberbullying with and without depressive symptoms. The current study analysed the relationship between positive personal resources and clinical symptoms in 251 adolescent victims of cyberbullying at several Spanish high schools. It examined how several positive personal resources varied in adolescent victims of cyberbullying who displayed symptoms of depression (n = 89) or did not (n = 162). Victims of cyberbullying who displayed depressive symptoms reported lower levels of personal resources (emotional intelligence, gratitude, optimism, and forgiveness) than those who did not. Logistic regression provided evidence that gratitude was the strongest predictor of depressive symptoms in victims of cyberbullying, followed by emotional intelligence and optimism. These findings expand the existing literature on the role of personal resources in mental health and highlight the need for their development in youths to help them cope more effectively and function better after being cyberbullied.

scholarly journals Expression of CD markers in JAK2V617F positive myeloproliferative neoplasms: Prognostic significance

2018 ◽  
Author(s):  
Saeid Shahrabi ◽  
Ali Ehsanpour ◽  
Somayyeh Heidary ◽  
Mohammad Shahjahani ◽  
Masumeh Maleki Behzad
Keyword(s):  
Clinical Outcomes ◽  
Prognostic Biomarker ◽  
Myeloproliferative Neoplasms ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Leukemic Transformation ◽  
And Function ◽  
The Relationship ◽  
Cd Markers

Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by the presence of JAK2V617F mutation. Thrombohemorrhagic as well as autoimmune or inflammatory phenomena are common clinical outcomes of these disorders. Recent studies have shown that abnormality in frequency and function of blood cells manifested by an alteration in CD markers’ expression patterns play a key role in these complications. So, there may be a relationship between CD markers’ expressions and prognosis of JAK2V617F positive MPNs. Therefore, in this review, we have focused on these abnormalities from the perspective of changing expressions of CD markers and assessment of the relationship between these changes with prognosis of JAK2V617F positive MPNs. It can be stated that the abnormal expression of a large number of CD markers can be used as a prognostic biomarker for clinical outcomes including thrombohememorrhagic events, as well as autoimmune and leukemic transformation in JAK2V617F positive MPNs. Considering the possible role of CD markers’ expressions in JAK2V617F MPNs prognosis, further studies are needed to confirm the relationship between the expression of CD markers with prognosis to be able to find an appropriate therapeutic approach via targeting CD markers.

scholarly journals Albino mutants of Streptomyces glaucescens tyrosinase

1991 ◽  
Vol 274 (3) ◽  
pp. 707-713 ◽  
Author(s):  
M P Jackman ◽  
A Hajnal ◽  
K Lerch
Keyword(s):  
Active Site ◽  
Critical Role ◽  
Site Directed Mutagenesis ◽  
Mutant Proteins ◽  
Carbonyl Derivatives ◽  
Hydrogen Bonding Interactions ◽  
Albino Phenotype ◽  
Derivatives Of ◽  
Streptomyces Glaucescens

Site-directed mutagenesis was used to determine the functional role of several residues of Streptomyces glaucescens tyrosinase. Replacement of His-37, -53, -193 or -215 by glutamine yields albino phenotypes, as determined by expression on melanin-indicator plates. The purified mutant proteins display no detectable oxy-enzyme and increased Cu lability at the binuclear active site. The carbonyl derivatives of H189Q and H193Q luminesce, with lambda max. displaced more than 25 nm to a longer wavelength compared with native tyrosinase. The remaining histidine mutants display no detectable luminescence. The results are consistent with these histidine residues (together with His-62 and His-189 reported earlier) acting as Cu ligands in the Streptomyces glaucescens enzyme. Conservative substitution of the invariant Asn-190 by glutamine also gives an albino phenotype, no detectable oxy-enzyme and labilization of active-site Cu. The luminescence spectrum of carbonyl-N190Q, however, closely resembles that of the native enzyme under conditions promoting double Cu occupancy of the catalytic site. A critical role for Asn-190 in active-site hydrogen-bonding interactions is proposed.

Role of the amino acid invariants in the active site of MurG as evaluated by site-directed mutagenesis

Biochimie ◽  
2007 ◽  
Vol 89 (12) ◽  
pp. 1498-1508 ◽  
Author(s):  
Muriel Crouvoisier ◽  
Geneviève Auger ◽  
Didier Blanot ◽  
Dominique Mengin-Lecreulx
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis

scholarly journals The mechanism of action of dd-peptidases: the role of Threonine-299 and -301 in the Streptomyces R61 dd-peptidase

1994 ◽  
Vol 301 (2) ◽  
pp. 477-483 ◽  
Author(s):  
J M Wilkin ◽  
A Dubus ◽  
B Joris ◽  
J M Frère
Keyword(s):  
Amino Acids ◽  
Active Site ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Peptide Substrate ◽  
Binding Properties ◽  
Beta Lactamases ◽  
Penicillin Binding Proteins ◽  
Active Site Cavity

The side chains of residues Thr299 and Thr301 in the Streptomyces R61 DD-peptidase have been modified by site-directed mutagenesis. These amino acids are part of a beta-strand which forms a wall of the active-site cavity. Thr299 corresponds to the second residue of the Lys-Thr(Ser)-Gly triad, highly conserved in active-site beta-lactamases and penicillin-binding proteins (PBPs). Modification of Thr301 resulted only in minor alterations of the catalytic and penicillin-binding properties of the enzyme. No selective decrease of the rate of acylation was observed for any particular class of compounds. By contrast, the loss of the hydroxy group of the residue in position 299 yielded a seriously impaired enzyme. The rates of inactivation by penicillins were decreased 30-50-fold, whereas the reactions with cephalosporins were even more affected. The efficiency of hydrolysis against the peptide substrate was also seriously decreased. More surprisingly, the mutant was completely unable to catalyse transpeptidation reactions. The conservation of an hydroxylated residue in this position in PBPs is thus easily explained by these results.

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