AI Article Synopsis
- N-Terminal methyltransferase 1 (NTMT1) plays a crucial role in modifying proteins by adding methyl groups to their N-terminus after methionine is removed, which is important for various cellular functions.
- Aberrant activity of NTMT1 has been linked to several cancers and developmental disorders, highlighting its significance in health and disease.
- Research using CRISPR-Cas9 knock-out cells identified OLA1 as a key protein affected by NTMT1 methylation, alongside the discovery of 72 potential targets through advanced profiling techniques.
Article Abstract
N-Terminal methyltransferase 1 (NTMT1) catalyzes the N-terminal methylation of proteins with a specific N-terminal motif after methionine removal. Aberrant N-terminal methylation has been implicated in several cancers and developmental diseases. Together with motif sequence and signal peptide analyses, activity-based substrate profiling of NTMT1 utilizing ()-hex-2-en-5-ynyl--adenosyl-l-methionine (Hey-SAM) revealed 72 potential targets, which include several previously confirmed ones and many unknowns. Target validation using normal and NTMT1 knock-out (KO) HEK293FT cells generated by CRISPR-Cas9 demonstrated that Obg-like ATPase 1 (OLA1), a protein involved in many critical cellular functions, is methylated by NTMT1. Additionally, Hey-SAM synthesis achieved ≥98% yield for SAH conversion.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889141 | PMC |
| http://dx.doi.org/10.1039/c9sc02550b | DOI Listing |
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Article Synopsis
- N-Terminal methyltransferase 1 (NTMT1) plays a crucial role in modifying proteins by adding methyl groups to their N-terminus after methionine is removed, which is important for various cellular functions.
- Aberrant activity of NTMT1 has been linked to several cancers and developmental disorders, highlighting its significance in health and disease.
- Research using CRISPR-Cas9 knock-out cells identified OLA1 as a key protein affected by NTMT1 methylation, alongside the discovery of 72 potential targets through advanced profiling techniques.
Molecular basis for histone N-terminal methylation by NRMT1.
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November 2015
MOE Key Laboratory of Protein Sciences, Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates. Here, we report the crystal structure of human NRMT1 bound to CENP-A peptide at 1.3 Å.
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