ArticleThe Journal of biological chemistry2015
Comparison of the enzymatic and functional properties of three cytosolic carboxypeptidase family members.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- Tubulin monoglutamylation is sufficient to rescue the ciliary motility defects in aFrontiers in cell and developmental biology · 2026Article
- AAV-based gene therapy ameliorates neurological deficits in a mouse model of childhood-onset neurodegeneration with cerebellar atrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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- Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.Journal of cellular and molecular medicine · 2024Article
- The distinct initiation sites and processing activities of TTLL4 and TTLL7 in glutamylation of brain tubulin.The Journal of biological chemistry · 2023Article
- Glutamylation is a negative regulator of microtubule growth.Molecular biology of the cell · 2023Article
- CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis.BMC biology · 2023Article
- Deciphering the Tubulin Language: Molecular Determinants and Readout Mechanisms of the Tubulin Code in Neurons.International journal of molecular sciences · 2023Review
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- TTLL1 and TTLL4 polyglutamylases are required for the neurodegenerative phenotypes in pcd mice.PLoS genetics · 2022Article
- The Childhood-Onset Neurodegeneration with Cerebellar Atrophy (CONDCA) Disease Caused byBiomedicines · 2021Review
- Article
- The Emerging Roles of Axonemal Glutamylation in Regulation of Cilia Architecture and Functions.Frontiers in cell and developmental biology · 2021Review
- Role of Cytosolic Carboxypeptidase 5 in Neuronal Survival and Spermatogenesis.Scientific reports · 2017Article
- Effects of Glycosylation on the Enzymatic Activity and Mechanisms of Proteases.International journal of molecular sciences · 2016Review
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Nna1 (CCP1) defines a subfamily of M14 metallocarboxypeptidases (CCP1-6) and is mutated in pcd (Purkinje cell degeneration) mice. Nna1, CCP4, and CCP6 are involved in the post-translational process of polyglutamylation, where they catalyze the removal of polyglutamate side chains. However, it is unknown whether these three cytosolic carboxypeptidases share identical enzymatic properties and redundant biological functions. We show that like Nna1, purified recombinant CCP4 and CCP6 deglutamylate tubulin, but unlike Nna1, neither rescues Purkinje cell degeneration in pcd mice, indicating that they do not have identical functions. Using biotin-based synthetic substrates, we established that the three enzymes are distinguishable based upon individual preferences for glutamate chain length, the amino acid immediately adjacent to the glutamate chain, and whether their activity is enhanced by nearby acidic amino acids. Nna1 and CCP4 remove the C-terminal glutamate from substrates with two or more glutamates, whereas CCP6 requires four or more glutamates. CCP4 behaves as a promiscuous glutamase, with little preference for chain length or neighboring amino acid composition. Besides glutamate chain length dependence, Nna1 and CCP6 exhibit higher k(cat)/K(m) when substrates contain nearby acidic amino acids. All cytosolic carboxypeptidases exhibit a monoglutamase activity when aspartic acid precedes a single glutamate, which, together with their other individual preferences for flanking amino acids, greatly increases the potential substrates for these enzymes and the biological processes in which they act. Additionally, Nna1 metabolized substrates mimicking the C terminus of tubulin in a way suggesting that the tyrosinated form of tubulin will accumulate in pcd mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.