Enzymes within a family often catalyze different reactions. In some cases, this variety stems from different catalytic machinery, but in other cases the machinery is identical; nevertheless, the enzymes catalyze different reactions. In this review, we examine the subset of α/β-hydrolase fold enzymes that contain the serine-histidine-aspartate catalytic triad. In spite of having the same protein fold and the same core catalytic machinery, these enzymes catalyze seventeen different reaction mechanisms. The most common reactions are hydrolysis of C-O, C-N and C-C bonds (Enzyme Classification (EC) group 3), but other enzymes are oxidoreductases (EC group 1), acyl transferases (EC group 2), lyases (EC group 4) or isomerases (EC group 5). Hydrolysis reactions often follow the canonical esterase mechanism, but eight variations occur where either the formation or cleavage of the acyl enzyme intermediate differs. The remaining eight mechanisms are lyase-type elimination reactions, which do not have an acyl enzyme intermediate and, in four cases, do not even require the catalytic serine. This diversity of mechanisms from the same catalytic triad stems from the ability of the enzymes to bind different substrates, from the requirements for different chemical steps imposed by these new substrates and, only in about half of the cases, from additional hydrogen bond partners or additional general acids/bases in the active site. This detailed analysis shows that binding differences and non-catalytic residues create new mechanisms and are essential for understanding and designing efficient enzymes.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455348PMC
http://dx.doi.org/10.1021/acscatal.5b01539DOI Listing

Publication Analysis

Top Keywords

catalytic machinery
12
catalytic triad
12
core catalytic
8
serine-histidine-aspartate catalytic
8
α/β-hydrolase fold
8
enzymes
8
fold enzymes
8
catalyze reactions
8
enzymes catalyze
8
acyl enzyme
8

Similar Publications

Nipah virus is a highly virulent zoonotic paramyxovirus causing severe respiratory and neurological disease. Despite its lethality, there is no approved treatment for Nipah virus infection. The viral polymerase complex, composed of the polymerase (L) and phosphoprotein (P), replicates and transcribes the viral RNA genome.

View Article and Find Full Text PDF

Viral proteases play critical roles in the host cell and immune remodeling that allows virus production. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) papain-like protease (PLpro) encoded in the large nonstructural protein 3 (Nsp3) also possesses isopeptidase activity with specificity for ubiquitin and ISG15 conjugates. Here, we interrogated the cellular interactome of the SARS-CoV-2 PLpro catalytic domain to gain insight into the putative substrates and cellular functions affected by the viral deubiquitinase.

View Article and Find Full Text PDF

Operando bonding nickel thiolate with CdS as efficient photocatalyst for hydrogen evolution.

J Colloid Interface Sci

December 2024

Key Laboratory of Green Chemical Process of Ministry of Education, School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205, PR China. Electronic address:

Employing metallic nanoclusters as cocatalysts for semiconductor-based photocatalysts and understanding their roles in enhancing photocatalytic performance is crucial. Herein, a nickel thiolate with cyclohexanethiol as the ligands (i.e.

View Article and Find Full Text PDF

HDAC10 switches NLRP3 modification from acetylation to ubiquitination and attenuates acute inflammatory diseases.

Cell Commun Signal

December 2024

Department of Immunology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, 250012, China.

Background: The NOD-like receptor protein (NLRP)3 inflammasome is at the signaling hub center to instigate inflammation in response to pathogen infection or oxidative stress, and its tight control is pivotal for immune defense against infection while avoiding parallel intensive inflammatory tissue injury. Acetylation of NLRP3 is critical for the full activation of NLRP3 inflammasome, while the precise regulation of the acetylation and deacetylation circuit of NLRP3 protein remained to be fully understood.

Methods: The interaction between histone deacetylase 10 (HDAC10) and NLRP3 was detected by immunoprecipitation and western blot in the HDAC10 and NLRP3 overexpressing cells.

View Article and Find Full Text PDF

The average eukaryotic tRNA contains 13 posttranscriptional modifications; however, their functional impact is largely unknown. Our understanding of the complex tRNA aminoacylation machinery in metazoans also remains limited. Herein, using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we provide the mechanistic basis for recognition and aminoacylation of fully-modified cellular tRNA by human lysyl-tRNA synthetase (h-LysRS).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!