Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (641 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Catalytic Domains; Domain, Catalytic; Domains, Catalytic; Catalytic Core; Catalytic Cores; Core, Catalytic; Cores, Catalytic; Catalytic Region.
Where it fits in the MeSH classification
- Broader topics
- Binding Sites; Protein Domains
Research landscape
PubMed indexes 36,598 records tagged with the MeSH heading “Catalytic Domain” (counts retrieved 2026-10-29). 7,322 of them (20.0%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 19,112 records.
Reviews account for 2,180 records (6.0%) and meta-analyses for 3. Randomized controlled trials number 6 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 630 |
| 2000-2009 | 9,534 |
| 2010-2019 | 19,112 |
| 2020 onward | 7,322 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,180 | 6.0% |
| Meta-analyses | 3 | 0.0% |
| Randomized controlled trials | 6 | 0.0% |
Method: PubMed query "Catalytic Domain"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease | 2021 | Research article Design not recorded in structured metadata | 308 | cc by PMID 33811162 · DOI · PMC8224385 |
| Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking | 2021 | Research article Design not recorded in structured metadata | 179 | cc by PMID 33853786 · DOI · PMC8046379 |
| Crystal structure of an RNA-cleaving DNAzyme | 2017 | Research article Design not recorded in structured metadata | 140 | cc by PMID 29222499 · DOI · PMC5722873 |
| ASMC: investigating the amino acid diversity of enzyme active sites | 2025 | Research article Design not recorded in structured metadata | 1 | cc by PMID 40372409 · DOI · PMC12133276 |
X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering.
- Closing excerpt
- We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (126 words)
The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33811162 · DOI · PMC8224385
Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling.
- Closing excerpt
- The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33853786 · DOI · PMC8046379
Crystal structure of an RNA-cleaving DNAzyme [3]
Abstract reading summary — source excerpts
- Opening excerpt
- In addition to storage of genetic information, DNA can also catalyze various reactions.
- Closing excerpt
- Our studies reveal that DNA is capable of forming a compacted structure and that the functionality-limited bio-polymer can have a novel solution for a functional need in catalysis.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (154 words)
In addition to storage of genetic information, DNA can also catalyze various reactions. RNA-cleaving DNAzymes are the catalytic DNAs discovered the earliest, and they can cleave RNAs in a sequence-specific manner. Owing to their great potential in medical therapeutics, virus control, and gene silencing for disease treatments, RNA-cleaving DNAzymes have been extensively studied; however, the mechanistic understandings of their substrate recognition and catalysis remain elusive. Here, we report three catalytic form 8-17 DNAzyme crystal structures. 8-17 DNAzyme adopts a V-shape fold, and the Pb2+ cofactor is bound at the pre-organized pocket. The structures with Pb2+ and the modification at the cleavage site captured the pre-catalytic state of the RNA cleavage reaction, illustrating the unexpected Pb2+-accelerated catalysis, intrinsic tertiary interactions, and molecular kink at the active site. Our studies reveal that DNA is capable of forming a compacted structure and that the functionality-limited bio-polymer can have a novel solution for a functional need in catalysis.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29222499 · DOI · PMC5722873
ASMC: investigating the amino acid diversity of enzyme active sites [4]
Abstract reading summary — source excerpts
- Opening excerpt
- MotivationThe analysis of enzyme active sites is essential for understanding their activity in terms of catalyzed reaction and substrate specificity, providing insights for engineering to obtain targeted properties or modify the substrate scope.
- Closing excerpt
- com/labgem/ASMC, along with a complete documentation (wiki, tutorial).
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (212 words)
MotivationThe analysis of enzyme active sites is essential for understanding their activity in terms of catalyzed reaction and substrate specificity, providing insights for engineering to obtain targeted properties or modify the substrate scope. In 2010, a first version of the Active Site Modeling and Clustering (ASMC) workflow was published. ASMC predicts isofunctional clusters from enzyme families, based on structural modeling and clustering of active sites. Since then, structure- and sequence-based methods have developed considerably.ResultsWe present here a redesign of the ASMC workflow. This new major version includes recent pocket prediction, structural alignment and clustering methods, as well as a refined amino acid distance matrix, thereby improving the relevance of results and reducing the need for laborious manual analysis to obtain relevant clusters. In addition, we have implemented multiple sequence alignment as a possible input for the clustering step, along with an additional script to compare 2D and 3D active sites. Finally, the code has been unified from three to one programming language (Python) to facilitate its installation and maintenance. This new version of ASMC was evaluated on a set of protein families, resulting in overall better performances compared to its original version.Availability and implementationASMC is supported on Linux operating system and freely available at https://github.com/labgem/ASMC, along with a complete documentation (wiki, tutorial).
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40372409 · DOI · PMC12133276
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Protein phosphatase 1--targeted in many directions [5]
- Research article The pyruvate dehydrogenase complexes: structure-based function and regulation [6]
- Research article The extended PP1 toolkit: designed to create specificity [7]
- Research article Structural basis of perturbed pKa values of catalytic groups in enzyme active sites [8]
- Research article The structural basis for control of eukaryotic protein kinases [9]
- Research article Structural and catalytic diversity within the amidohydrolase superfamily [10]
References
- Günther S, Reinke PYA, Fernández-García Y, Lieske J, Lane TJ, Ginn HM, et al.. X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease. . 2021. PMID 33811162 · DOI · PMC8224385
- Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, et al.. Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking. . 2021. PMID 33853786 · DOI · PMC8046379
- Liu H, Yu X, Chen Y, Zhang J, Wu B, Zheng L, et al.. Crystal structure of an RNA-cleaving DNAzyme. . 2017. PMID 29222499 · DOI · PMC5722873
- Bailly T, Elisée E, Vallenet D. ASMC: investigating the amino acid diversity of enzyme active sites. . 2025. PMID 40372409 · DOI · PMC12133276
- Cohen PT. Protein phosphatase 1--targeted in many directions. J Cell Sci. 2002. PMID 11839776 · DOI
- Patel MS, Nemeria NS, Furey W, Jordan F. The pyruvate dehydrogenase complexes: structure-based function and regulation. J Biol Chem. 2014. PMID 24798336 · DOI · PMC4059105
- Bollen M, Peti W, Ragusa MJ, Beullens M. The extended PP1 toolkit: designed to create specificity. Trends Biochem Sci. 2010. PMID 20399103 · DOI · PMC3131691
- Harris TK, Turner GJ. Structural basis of perturbed pKa values of catalytic groups in enzyme active sites. IUBMB Life. 2002. PMID 12049200 · DOI
- Endicott JA, Noble ME, Johnson LN. The structural basis for control of eukaryotic protein kinases. Annu Rev Biochem. 2012. PMID 22482904 · DOI
- Seibert CM, Raushel FM. Structural and catalytic diversity within the amidohydrolase superfamily. Biochemistry. 2005. PMID 15850372 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.