6C4S

Human cSrc SH3 Domain in complex with Choline Kinase fragment 60-69

Summary for 6C4S

• Entry DOI: 10.2210/pdb6c4s/pdb
• Descriptor: Proto-oncogene tyrosine-protein kinase Src,cSrc SH3 Domain, ZINC ION (3 entities in total)
• Functional Keywords: enzyme, non-receptor tyrosine kinase, peptide binding protein, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 16466.97

Authors

Kall, S.L.,Lavie, A. (deposition date: 2018-01-12, release date: 2019-01-23, Last modification date: 2024-03-13)

Primary citation

Kall, S.L.,Whitlatch, K.,Smithgall, T.E.,Lavie, A.
Molecular basis for the interaction between human choline kinase alpha and the SH3 domain of the c-Src tyrosine kinase.
Sci Rep, 9:17121-17121, 2019

PubMed Abstract: Choline kinase alpha is a 457-residue protein that catalyzes the reaction between ATP and choline to yield ADP and phosphocholine. This metabolic action has been well studied because of choline kinase's link to cancer malignancy and poor patient prognosis. As the myriad of x-ray crystal structures available for this enzyme show, chemotherapeutic drug design has centered on stopping the catalytic activity of choline kinase and reducing the downstream metabolites it produces. Furthermore, these crystal structures only reveal the catalytic domain of the protein, residues 80-457. However, recent studies provide evidence for a non-catalytic protein-binding role for choline kinase alpha. Here, we show that choline kinase alpha interacts with the SH3 domain of c-Src. Co-precipitation assays, surface plasmon resonance, and crystallographic analysis of a 1.5 Å structure demonstrate that this interaction is specific and is mediated by the poly-proline region found N-terminal to the catalytic domain of choline kinase. Taken together, these data offer strong evidence that choline kinase alpha has a heretofore underappreciated role in protein-protein interactions, which offers an exciting new way to approach drug development against this cancer-enhancing protein.

PubMed: 31745227
DOI: 10.1038/s41598-019-53447-0

Experimental method

X-RAY DIFFRACTION (1.5 Å)