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Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites

António J M Ribeiro, Gemma L Holliday, Nicholas Furnham, Jonathan D Tyzack, Katherine Ferris, Janet M Thornton
2017 Nucleic Acids Research  
M-CSA (Mechanism and Catalytic Site Atlas) is a database of enzyme active sites and reaction mechanisms that can be accessed at www.ebi.ac.uk/ thornton-srv/m-csa.  ...  M-CSA results from the merging of two existing databases, MACiE (Mechanism, Annotation and Classification in Enzymes), a database of enzyme mechanisms, and CSA (Catalytic Site Atlas), a database of catalytic  ...  ACKNOWLEDGEMENTS The authors would like to thank Neera Borkakoti, Roman Laskowski and John Mitchell for helpful discussions.  ... 
doi:10.1093/nar/gkx1012 pmid:29106569 pmcid:PMC5753290 fatcat:sep5alggufdb7msnnlsx47dlmq

A global analysis of function and conservation of catalytic residues in enzymes

António J. M. Ribeiro, Jonathan D. Tyzack, Neera Borkakoti, Gemma L. Holliday, Janet M. Thornton
2019 Journal of Biological Chemistry  
Here, we review the data on the catalytic residues of 648 enzymes, as annotated in the Mechanism and Catalytic Site Atlas (M-CSA), and compare our results with those in previous studies.  ...  The catalytic residues of an enzyme comprise the amino acids located in the active center responsible for accelerating the enzyme-catalyzed reaction.  ...  Enzymes (MACiE), a database of enzyme mechanisms (22, 23) , and Catalytic Site Atlas (CSA) (22, 23) , a database of catalytic sites (24, 25) .  ... 
doi:10.1074/jbc.rev119.006289 pmid:31796628 pmcid:PMC6956550 fatcat:umxyfl7xvzbkngv6nuwrvghboy

Graph Transformation for Enzymatic Mechanisms [article]

Jakob L. Andersen, Rolf Fagerberg, Christoph Flamm, Walter Fontana, Juraj Kolčák, Christophe V.F.P. Laurent, Daniel Merkle, Nikolai Nøjaard
2021 arXiv   pre-print
We derive about 1000 rules for amino acid side chain chemistry from the M-CSA database, a curated repository of enzymatic mechanisms.  ...  Using graph transformation we are able to propose hundreds of hypothetical catalytic mechanisms for a large number of unrelated reactions in the Rhea database.  ...  Acknowledgments The authors gratefully acknowledge Leon Middelboe Hansen and Mikkel Pilegaard for providing scripts constituting the preliminary analysis of the rules.  ... 
arXiv:2102.03292v2 fatcat:2bpmmjmuynapbcl4ddt56b3bki

Graph transformation for enzymatic mechanisms

Jakob L Andersen, Rolf Fagerberg, Christoph Flamm, Walter Fontana, Juraj Kolčák, Christophe V F P Laurent, Daniel Merkle, Nikolai Nøjgaard
2021 Bioinformatics  
We derive about 1000 rules for amino acid side chain chemistry from the M-CSA database, a curated repository of enzymatic mechanisms.  ...  Using graph transformation, we are able to propose hundreds of hypothetical catalytic mechanisms for a large number of unrelated reactions in the Rhea database.  ...  Acknowledgements The authors gratefully acknowledge Leon Middelboe Hansen and Mikkel Pilegaard for providing scripts constituting the preliminary analysis of the rules.  ... 
doi:10.1093/bioinformatics/btab296 pmid:34252947 pmcid:PMC8686676 fatcat:bdnijoqtjvgunm4wlbbunib43u

Representing catalytic mechanisms with rule composition [article]

Jakob L. Andersen, Rolf Fagerberg, Christoph Flamm, Walter Fontana, Juri Kolčák, Christophe V.F.P. Laurent, Daniel Merkle, Nikolai Nøjgaard
2022 arXiv   pre-print
In a first application, we exploit mechanistic information in the Mechanism and Catalytic Site Atlas to construct overlay graphs of hydrolase reactions listed in the database.  ...  These graphs point at a spectrum of catalytic entanglement of enzyme and substrate, de-emphasizing the notion of a singular catalyst in favor of a collection of catalytic sites that can be distributed  ...  Acknowledgments This work is supported by the Novo Nordisk Foundation grant NNF19OC0057834 and by the Independent Research Fund Denmark, Natural Sciences, grants DFF-0135-00420B and DFF-7014-00041.  ... 
arXiv:2201.04515v2 fatcat:xx5uwzh4s5cj7hezlu7daq3oga

Machine Learning Differentiates Enzymatic and Non-Enzymatic Metals in Proteins [article]

Ryan Feehan, Meghan W. Franklin, Joanna Sarah Gershkoff Slusky
2021 bioRxiv   pre-print
Identifying enzyme active sites is an important task in enzymology. Metalloenzymes are 40% of all enzymes and can perform all seven classes of enzyme reactions.  ...  The ability of our model to correctly identify which metal sites are responsible for enzymatic activity could assist with identifying new enzymatic mechanisms or designing de novo enzymes.  ...  Acknowledgments: We gratefully acknowledge helpful conversations and manuscript edits from members of the Slusky lab as well as Yusuf Adeshina, and Adam Pogorny, We appreciate Patrick Mahomes for inspiring  ... 
doi:10.1101/2021.02.01.429261 fatcat:f6jfwkitejei3nnw5yamb3ncxa

EnzyMine: a comprehensive database for enzyme function annotation with enzymatic reaction chemical feature

Dandan Sun, Xingxiang Cheng, Yu Tian, Shaozhen Ding, Dachuan Zhang, Pengli Cai, Qian-nan Hu
2020 Database: The Journal of Biological Databases and Curation  
Therefore, global mining of enzymatic reactions will offer a unique landscape for researchers to understand the basic functional mechanisms of natural bioprocesses and facilitate enzyme function annotation  ...  EnzyMine represents an advanced database that extends enzyme knowledge by incorporating reaction chemical feature strategies, strengthening the connectivity between enzyme and metabolic reactions.  ...  A specific collection of catalytic residues and detailed processes of catalytic mechanisms can be obtained from M-CSA (7) .  ... 
doi:10.1093/database/baaa065 pmid:33002112 fatcat:kcbu33zg4baenj5yrcrohclxqe

Machine learning differentiates enzymatic and non-enzymatic metals in proteins

Ryan Feehan, Meghan W. Franklin, Joanna S. G. Slusky
2021 Nature Communications  
AbstractMetalloenzymes are 40% of all enzymes and can perform all seven classes of enzyme reactions.  ...  We anticipate that our model's ability to correctly identify which metal sites are responsible for enzymatic activity could enable identification of new enzymatic mechanisms and de novo enzyme design.  ...  Acknowledgements We gratefully acknowledge helpful conversations and paper edits from members of the Slusky lab as well as Yusuf Adeshina and Adam Pogorny.  ... 
doi:10.1038/s41467-021-24070-3 pmid:34140507 fatcat:oy2vjdj7xfblzgseg73jvmg3ba

Capturing the geometry, function, and evolution of enzymes with 3D templates [article]

Ioannis G. Riziotis, Janet M. Thornton
2022 arXiv   pre-print
Therefore, we anticipate that template-based functional site detection will be a powerful tool in the task of characterising a vast number of new protein models.  ...  Structural templates are 3D signatures representing protein functional sites, such as ligand binding cavities, metal coordination motifs or catalytic sites.  ...  Acknowledgements The work was supported by: the EMBL International PhD Programme (IGR) and the European Molecular Biology Laboratory (JMT)  ... 
arXiv:2203.02687v1 fatcat:jho4o75vuzd3xmwjmuemi2ddea

A strategy for large-scale comparison of evolutionary- and reaction-based classifications of enzyme function

Gemma L Holliday, Shoshana D Brown, David Mischel, Benjamin J Polacco, Patricia C Babbitt
2020 Database: The Journal of Biological Databases and Curation  
Historically, classification of enzyme reactions has used the enzyme nomenclature system developed to describe the overall reactions performed by biochemically characterized enzymes, irrespective of their  ...  of sequences of unknown function represented in major databases.  ...  helpful discussions about the design and implementation of the comparison strategy, Jeffrey Yunes for useful discussions regarding code development for generating networks and Kathy Clement for help with  ... 
doi:10.1093/database/baaa034 pmid:32449511 fatcat:fnfgcszyqjfttb7ulzllwir2am

Structure-Based Survey of the Human Proteome for Opportunities in Proximity Pharmacology [article]

Evianne Rovers, Matthieu Schapira
2022 bioRxiv   pre-print
To survey the human proteome for opportunities in proximity pharmacology, we systematically mapped non-catalytic drug binding pockets on the structure of protein-modifying enzymes available from the Protein  ...  The concept can be expanded to induce other post-translational modifications via the recruitment of different types of protein-modifying enzymes.  ...  Mechanism and Catalytic Site Atlas (M-CSA): A Database of Enzyme Reaction Mechanisms and Active Sites. Nucleic Acids Res. 2018, 46 (D1), D618-D623. (16) Bateman, A.; Martin, M.  ... 
doi:10.1101/2022.01.13.475779 fatcat:ji2ezy2okrbdppftw74jgkgwnm

Quantifying evolutionary importance of protein sites: A Tale of two measures

Avital Sharir-Ivry, Yu Xia, Jianzhi Zhang
2021 PLoS Genetics  
The unique requirement for the active site to selectively stabilize the transition state of the catalyzed chemical reaction imposes additional selective constraints on the rest of the enzyme.  ...  Surprisingly however, catalytic sites in enzymes are the principal exception to this rule.  ...  We identified catalytic sites using the Mechanism and Catalytic Site Atlas (M-CSA) [20] , ligand-binding sites using BioLip [21] , allosteric sites using the Allosteric Database (ASD) [22] [23] [24]  ... 
doi:10.1371/journal.pgen.1009476 pmid:33826605 fatcat:lz5exn4vnzaylnhr4pr4bjmw5m

Highlighting Human Enzymes Active in Different Metabolic Pathways and Diseases: The Case Study of EC 1.2.3.1 and EC 2.3.1.9

Giulia Babbi, Davide Baldazzi, Castrense Savojardo, Martelli Pier Luigi, Rita Casadio
2020 Biomedicines  
We perform a statistics to derive our present knowledge on human metabolic pathways (the Kyoto Encyclopaedia of Genes and Genomes (KEGG)), and we found that activity aldehyde dehydrogenase (NAD(+)), described  ...  sites.  ...  Several databases are presently available for enzyme complete functional annotation, including BRENDA [16] , Enzyme Portal (EBI) [17] , and M-CSA (EBI) [18] .  ... 
doi:10.3390/biomedicines8080250 pmid:32751059 fatcat:3rk2d22brrfpveemmpkxwf4duq

A roadmap for metagenomic enzyme discovery

Serina L. Robinson, Jörn Piel, Shinichi Sunagawa
2021 Natural product reports (Print)  
Here we review computational and experimental strategies to discover biosynthetic enzymes from metagenomes.  ...  Shotgun metagenomic approaches to uncover new enzymes are underdeveloped relative to PCR- or activity-based functional metagenomics.  ...  s lab has been supported by grants of the Swiss National Science Foundation (205321_184955), the NCCR Microbiomes (51NF40_180575) and the ETH domain (PHRT #521).  ... 
doi:10.1039/d1np00006c pmid:34821235 pmcid:PMC8597712 fatcat:43y3eqguw5ex5ikz7ihs7r3lg4

Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

Dasol Kim, Hui-Yun Hwang, Eun Sun Ji, Jin Young Kim, Jong Shin Yoo, Ho Jeong Kwon
2021 Communications Biology  
To elucidate the mechanism underlying Kaem's biological activity, the target protein was identified via combined drug affinity responsive target stability and LC–MS/MS analyses.  ...  AbstractDisorders of autophagy, a key regulator of cellular homeostasis, cause a number of human diseases.  ...  ), and by the Brain Korea 21 Plus Project and ICONS (Institute of Convergence Science), Yonsei University.  ... 
doi:10.1038/s42003-020-01566-0 pmid:33398033 fatcat:fftuh5fn4fgzdmcoskta5cw7na