ROCO Kinase Activity Is Controlled by Internal GTPase Function (Interactive Structures)

Bertram Weiss¹*

¹ Target Research, Bayer Schering Pharma AG13342, Berlin, Germany.

*Corresponding author. E-mail, bertram.weiss{at}bayerhealthcare.com

Interactive Image 1. Homodimers of the ROC domains of human leucine-rich repeat kinase 2 (LRRK2). This structure is based on PDB entry 2ZEJ and visualized with JMOL (1). This is an interactive version of the molecular structure shown in Figure 2A. One ROC domain is shown as yellow, the other as green. GDP is shown as a ball-and-stick representation with a red transparent surface. Mg2+ surface is in blue.

Interactive Image 2. Structure of the dimeric GTPase domains (1335-1512 amino acids) of LRRK2 based on the PDB database entry 2ZEJ . This is an interactive version of the molecular structure shown in Figure 2B. Solid ribbon representation of the subunits with the four amino acids F1401, P1406, W1434, and R1441 of each monomer shown as ball and stick in the corresponding color.

Interactive Image 3. Similar to Interactive Image 2 but with additional highlighting of the surface of the four amino acids of each monomer. This is an interactive version of the molecular structure shown in Figure 2C. Here, the zipper-like structure of the 8 alternating green and yellow amino acids is clearly visible and highlights how the dimer is glued together. In Parkinson's disease, R1441 is mutated and most likely disturbs the zipper which can be measured as reduced GTP hydrolysis activity.

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Reference

Citation: B. Weiss, ROCO Kinase Activity Is Controlled by Internal GTPase Function. Sci. Signal. 1, pe27 (2008).