Metal- and Serine-Dependent Meta-Cleavage Product Hydrolases Utilize Similar Nucleophile-Activation Strategies

ACS Catalysis ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 11622-11632 ◽  
Author(s):  
Eugene Kuatsjah ◽  
Anson C. K. Chan ◽  
Timothy E. Hurst ◽  
Victor Snieckus ◽  
Michael E. P. Murphy ◽  
...  
Keyword(s):  
Cleavage Product ◽  
Nucleophile Activation

Nucleophilic aromatic substitution using Et3SiH/cat. t-Bu-P4 as a system for nucleophile activation

2007 ◽  
pp. 2264 ◽  
Author(s):  
Masahiro Ueno ◽  
Misato Yonemoto ◽  
Masahiro Hashimoto ◽  
Andrew E. H. Wheatley ◽  
Hiroshi Naka ◽  
...  
Keyword(s):  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Nucleophile Activation

scholarly journals Metabolism of biphenyl. Structure and physicochemical properties of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid, the meta-cleavage product from 2,3-dihydroxybiphenyl by Pseudomonas putida

1974 ◽  
Vol 143 (2) ◽  
pp. 431-434 ◽  
Author(s):  
Danilo Catelani ◽  
Antonio Colombi
Keyword(s):  
Physicochemical Properties ◽  
Pseudomonas Putida ◽  
Dienoic Acid ◽  
Cleavage Product

The structure of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid for the meta-cleavage product of 2,3-dihydroxybiphenyl by a Pseudomonas putida strain was demonstrated on the basis of its chemical and physicochemical properties and those of its derivatives.

scholarly journals Furin Cleavage of L2 during Papillomavirus Infection: Minimal Dependence on Cyclophilins

2016 ◽  
Vol 90 (14) ◽  
pp. 6224-6234 ◽  
Author(s):  
Matthew P. Bronnimann ◽  
Christine M. Calton ◽  
Samantha F. Chiquette ◽  
Shuaizhi Li ◽  
Mingfeng Lu ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Current Model ◽  
Hpv Infection ◽  
Cleavage Product ◽  
Protein Domain ◽  
Furin Cleavage ◽  
Minor Capsid Protein ◽  
Papillomavirus Infection ◽  
Successful Infection ◽  
N Terminus

ABSTRACTDespite an abundance of evidence supporting an important role for the cleavage of minor capsid protein L2 by cellular furin, direct cleavage of capsid-associated L2 during human papillomavirus 16 (HPV16) infection remains poorly characterized. The conserved cleavage site, close to the L2 N terminus, confounds observation and quantification of the small cleavage product by SDS-PAGE. To overcome this difficulty, we increased the size shift by fusing a compact protein domain, thePropionibacterium shermaniitranscarboxylase domain (PSTCD), to the N terminus of L2. The infectious PSTCD-L2 virus displayed an appreciable L2 size shift during infection of HaCaT keratinocytes. Cleavage under standard cell culture conditions rarely exceeded 35% of total L2. Cleavage levels were enhanced by the addition of exogenous furin, and the absolute levels of infection correlated to the level of L2 cleavage. Cleavage occurred on both the HaCaT cell surface and extracellular matrix (ECM). Contrary to current models, experiments on the involvement of cyclophilins revealed little, if any, role for these cellular enzymes in the modulation of furin cleavage. HPV16 L2 contains two consensus cleavage sites, Arg5 (2RHKR5) and Arg12 (9RTKR12). Mutant PSTCD-L2 viruses demonstrated that although furin can cleave either site, cleavage must occur at Arg12, as cleavage at Arg5 alone is insufficient for successful infection. Mutation of the conserved cysteine residues revealed that the Cys22-Cys28 disulfide bridge is not required for cleavage. The PSTCD-L2 virus or similar N-terminal fusions will be valuable tools to study additional cellular and viral determinants of furin cleavage.IMPORTANCEFurin cleavage of minor capsid protein L2 during papillomavirus infection has been difficult to directly visualize and quantify, confounding efforts to study this important step of HPV infection. Fusion of a small protein domain to the N terminus greatly facilitates direct visualization of the cleavage product, revealing important characteristics of this critical process. Contrary to the current model, we found that cleavage is largely independent of cyclophilins, suggesting that cyclophilins act either in parallel to or downstream of furin to trigger exposure of a conserved N-terminal L2 epitope (RG-1) during infection. Based on this finding, we strongly caution against using L2 RG-1 epitope exposure as a convenient but indirect proxy of furin cleavage.

Differential Roles of Three Different Upper Pathway Meta Ring Cleavage Product Hydrolases in the Degradation of Dibenzo- p -dioxin and Dibenzofuran by Sphingomonas wittichii RW1

2021 ◽  
Author(s):  
Thamer Y. Mutter ◽  
Gerben J. Zylstra
Keyword(s):  
Gene Knockout ◽  
Sole Source ◽  
Cleavage Product ◽  
Ring Cleavage ◽  
Catabolic Pathway ◽  
Double Knockout ◽  
Cleavage Enzyme ◽  
Sphingomonas Wittichii ◽  
Physiological Approach

Sphingomonas wittichii RW1 grows on the two related compounds dibenzofuran (DBF) and dibenzo- p -dioxin (DXN) as the sole source of carbon. Previous work by others (P.V. Bunz, R. Falchetto, and A.M. Cook. Biodegradation 4:171-8, 1993, doi: 10.1007/BF00695119) identified two upper pathway meta cleavage product hydrolases (DxnB1 and DxnB2) active on the DBF upper pathway metabolite 2-hydroxy-6-oxo-6-(2-hydroxyphenyl)-hexa-2,4-dienoate. We took a physiological approach to determine the role of these two enzymes in the degradation of DBF and DXN by RW1. Single knockouts of either plasmid located dbfB1 or chromosome located dbfB2 had no effect on RW1 growth on either DBF or DXN. However, a double knockout lost the ability to grow on DBF but still grew normally on DXN demonstrating that DbfB1 and DbfB2 are the only hydrolases involved in the DBF upper pathway. Using a transcriptomic-guided approach we identified a constitutively expressed third hydrolase encoded by the chromosomally located SWIT0910 gene. Knockout of SWIT0910 resulted in a strain that no longer grows on DXN but still grows normally on DBF. Thus the DbfB1 and DbfB2 hydrolases function in the DBF but not the DXN catabolic pathway and the SWIT0190 hydrolase functions in the DXN but not the DBF catabolic pathway. Importance S. wittichii RW1 is one of only a few strains known to grow on DXN as the sole course of carbon. Much of the work deciphering the related RW1 DXN and DBF catabolic pathways has involved genome gazing, transcriptomics, proteomics, heterologous expression, and enzyme purification and characterization. Very little research has utilized physiological techniques to precisely dissect the genes and enzymes involved in DBF and DXN degradation. Previous work by others identified and extensively characterized two RW1 upper pathway hydrolases. Our present work demonstrates that these two enzymes are involved in DBF but not DXN degradation. In addition, our work identified a third constitutively expressed hydrolase that is involved in DXN but not DBF degradation. Combined with our previous work, this means that the RW1 DXN upper pathway involves genes from three very different locations in the genome: an initial plasmid-encoded dioxygenase and a ring cleavage enzyme and hydrolase encoded on opposite sides of the chromosome.

scholarly journals Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs.

1995 ◽  
Vol 15 (1) ◽  
pp. 235-245 ◽  
Author(s):  
W Scheper ◽  
D Meinsma ◽  
P E Holthuizen ◽  
J S Sussenbach
Keyword(s):  
Growth Factor ◽  
Long Range ◽  
Cleavage Site ◽  
Untranslated Region ◽  
Cleavage Product ◽  
Coding Region ◽  
Endonucleolytic Cleavage ◽  
Factor Ii ◽  
Sequence Elements ◽  
Rna Interaction

Human insulin-like growth factor II (IGF-II) mRNAs are subject to site-specific endonucleolytic cleavage in the 3' untranslated region, leading to an unstable 5' cleavage product containing the IGF-II coding region and a very stable 3' cleavage product of 1.8 kb. This endonucleolytic cleavage is most probably the first and rate-limiting step in degradation of IGF-II mRNAs. Two sequence elements within the 3' untranslated region are required for cleavage: element I, located approximately 2 kb upstream of the cleavage site, and element II, encompassing the cleavage site itself. We have identified a stable double-stranded RNA stem structure (delta G = -100 kcal/mol [418.4 kJ/mol]) that can be formed between element I and a region downstream of the cleavage site in element II. This structure is conserved among human, rat, and mouse mRNAs. Detailed analysis of the requirements for cleavage shows that the relative position of the elements is not essential for cleavage. Furthermore, the distance between the coding region and the cleavage site does not affect the cleavage reaction. Mutational analysis of the long-range RNA-RNA interaction shows that not only the double-stranded character but also the sequence of the stable RNA stem is important for cleavage.

The D:E complex as a discrete plasmic cleavage product of fibrinogen

1977 ◽  
Vol 10 (1) ◽  
pp. 175-181 ◽  
Author(s):  
Edward F. Plow ◽  
Czeslaw Cierniewski ◽  
Thomas S. Edgington
Keyword(s):  
Cleavage Product

P3-195: A TAU CLEAVAGE PRODUCT, ΔTAU314, IS INCREASED IN ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE WITH DEMENTIA

2006 ◽  
Vol 14 (7S_Part_21) ◽  
pp. P1141-P1142
Author(s):  
Benjamin R. Smith ◽  
Kathryn Nelson ◽  
Peng Liu ◽  
Margaret E. Flanagan ◽  
Dirk Keene ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cleavage Product ◽  
Parkinson’S Disease With Dementia ◽  
Tau Cleavage
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