The Structural Determinants Accounting for the Broad Substrate Specificity of the Quorum Quenching Lactonase GcL

ChemBioChem ◽  
2019 ◽  
Author(s):  
Celine Bergonzi ◽  
Michael Schwab ◽  
Tanushree Naik ◽  
Mikael Elias
Keyword(s):  
Substrate Specificity ◽  
Quorum Quenching ◽  
Structural Determinants ◽  
Broad Substrate Specificity

Investigation of Structural Determinants for the Substrate Specificity in the Zinc-Dependent Alcohol Dehydrogenase CPCR2 fromCandida parapsilosis

ChemBioChem ◽  
2015 ◽  
Vol 16 (10) ◽  
pp. 1512-1519 ◽  
Author(s):  
Christoph Loderer ◽  
Gaurao V. Dhoke ◽  
Mehdi D. Davari ◽  
Wolfgang Kroutil ◽  
Ulrich Schwaneberg ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Substrate Specificity ◽  
Structural Determinants

scholarly journals LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity

2006 ◽  
Vol 398 (3) ◽  
pp. 531-538 ◽  
Author(s):  
Yukiko Mizutani ◽  
Akio Kihara ◽  
Yasuyuki Igarashi
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Family Members ◽  
Fatty Acyl ◽  
Ceramide Synthase ◽  
Broad Substrate Specificity ◽  
Acid Protein ◽  
Amino Acid Protein

The LASS (longevity assurance homologue) family members are highly conserved from yeasts to mammals. Five mouse and human LASS family members, namely LASS1, LASS2, LASS4, LASS5 and LASS6, have been identified and characterized. In the present study we cloned two transcriptional variants of hitherto-uncharacterized mouse LASS3 cDNA, which encode a 384-amino-acid protein (LASS3) and a 419-amino-acid protein (LASS3-long). In vivo, [3H]dihydrosphingosine labelling and electrospray-ionization MS revealed that overproduction of either LASS3 isoform results in increases in several ceramide species, with some preference toward those having middle- to long-chain-fatty acyl-CoAs. A similar substrate preference was observed in an in vitro (dihydro)ceramide synthase assay. These results indicate that LASS3 possesses (dihydro)ceramide synthesis activity with relatively broad substrate specificity. We also found that, except for a weak display in skin, LASS3 mRNA expression is limited almost solely to testis, implying that LASS3 plays an important role in this gland.

scholarly journals TheArabidopsisAtSTE24 Is a CAAXProtease with Broad Substrate Specificity

2002 ◽  
Vol 277 (33) ◽  
pp. 29856-29864 ◽  
Author(s):  
Keren Bracha ◽  
Meirav Lavy ◽  
Shaul Yalovsky
Keyword(s):  
Substrate Specificity ◽  
Broad Substrate Specificity

scholarly journals Human and mouse granzyme M display divergent and species-specific substrate specificities

2011 ◽  
Vol 437 (3) ◽  
pp. 431-442 ◽  
Author(s):  
Stefanie A.H. de Poot ◽  
Marijn Westgeest ◽  
Daniel R. Hostetter ◽  
Petra van Damme ◽  
Kim Plasman ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Specific Substrate ◽  
Structural Determinants ◽  
Cytotoxic Lymphocyte ◽  
Potent Inducer ◽  
Methionine Residue ◽  
Positional Scanning ◽  
Methionine Residues ◽  
Species Specific ◽  
Positional Scanning Libraries

Cytotoxic lymphocyte protease GrM (granzyme M) is a potent inducer of tumour cell death and a key regulator of inflammation. Although hGrM (human GrM) and mGrM (mouse GrM) display extensive sequence homology, the substrate specificity of mGrM remains unknown. In the present study, we show that hGrM and mGrM have diverged during evolution. Positional scanning libraries of tetrapeptide substrates revealed that mGrM is preferred to cleave after a methionine residue, whereas hGrM clearly favours a leucine residue at the P1 position. The kinetic optimal non-prime subsites of both granzymes were also distinct. Gel-based and complementary positional proteomics showed that hGrM and mGrM have a partially overlapping set of natural substrates and a diverged prime and non-prime consensus cleavage motif with leucine and methionine residues being major P1 determinants. Consistent with positional scanning libraries of tetrapeptide substrates, P1 methionine was more frequently used by mGrM as compared with hGrM. Both hGrM and mGrM cleaved α-tubulin with similar kinetics. Strikingly, neither hGrM nor mGrM hydrolysed mouse NPM (nucleophosmin), whereas human NPM was hydrolysed efficiently by GrM from both species. Replacement of the putative P1′–P2′ residues in mouse NPM with the corresponding residues of human NPM restored cleavage of mouse NPM by both granzymes. This further demonstrates the importance of prime sites as structural determinants for GrM substrate specificity. GrM from both species efficiently triggered apoptosis in human but not in mouse tumour cells. These results indicate that hGrM and mGrM not only exhibit divergent specificities but also trigger species-specific functions.

Prediction of amino acid residues participated in substrate recognition by cytochrome P450 subfamilies with broad substrate specificity

2013 ◽  
Vol 26 (2) ◽  
pp. 86-91 ◽  
Author(s):  
Maria S. Zharkova ◽  
Boris N. Sobolev ◽  
Nina Yu. Oparina ◽  
Alexander V. Veselovsky ◽  
Alexander I. Archakov
Keyword(s):  
Cytochrome P450 ◽  
Amino Acid ◽  
Substrate Specificity ◽  
Substrate Recognition ◽  
Amino Acid Residues ◽  
Broad Substrate Specificity
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