Nucleoside-diphosphate kinase

Nucleoside-diphosphate kinase (NDPK) is an enzyme that plays a crucial role in the synthesis of nucleoside triphosphates (NTPs) other than adenosine triphosphate (ATP). It is involved in numerous cellular processes, including DNA replication, RNA transcription, and signal transduction, making it essential for cell growth and maintenance.

Function

NDPK functions by transferring the γ-phosphate group from a nucleoside triphosphate donor, such as ATP, to a nucleoside diphosphate acceptor, such as guanosine diphosphate (GDP), thus generating the corresponding nucleoside triphosphate, in this case, guanosine triphosphate (GTP). This reaction is critical for maintaining the cellular balance of NTPs, which are required for various biochemical processes.

Structure

The structure of NDPK is highly conserved across different species. It typically functions as a hexamer composed of identical or closely related subunits. Each subunit contains a nucleotide binding domain and a catalytic domain, which are necessary for the enzyme's activity.

Isoforms

In humans, several isoforms of NDPK have been identified, designated as NDPK-A, NDPK-B, and NDPK-C, among others. These isoforms are encoded by different genes and exhibit distinct tissue distributions and functions. For example, NDPK-A is ubiquitously expressed, while NDPK-B is more specific to certain tissues.

Clinical Significance

Alterations in the expression or activity of NDPK have been linked to various diseases, including cancer, where it may function as a metastasis suppressor or promoter, depending on the context. Additionally, mutations in the genes encoding NDPK isoforms have been associated with certain genetic disorders.

Research

Ongoing research aims to further elucidate the roles of NDPK in cellular processes and disease. Understanding the mechanisms by which NDPK functions could lead to the development of novel therapeutic strategies for treating diseases associated with its dysregulation.

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  Structure of Nucleoside-diphosphate kinase

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  Ping-Pong Mechanism of Nucleoside-diphosphate kinase

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  Nucleoside-diphosphate kinase ppGpp Cycle