3EU5

Crystal structure of FTase(ALPHA-subunit; BETA-subunit DELTA C10) in complex with BiotinGPP

Summary for 3EU5

• Entry DOI: 10.2210/pdb3eu5/pdb
• Related: 3EUV
• Descriptor: Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha, Protein farnesyltransferase subunit beta, ZINC ION, ... (5 entities in total)
• Functional Keywords: protein prenylation, prenylome analysis, prenyltransferase, transferase, metal-binding, phosphoprotein, zinc
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 92468.41

Authors

Guo, Z.,Nguyen, U.T.T.,Delon, C.,Bon, R.S.,Blankenfeldt, W.,Goody, R.S.,Waldmann, H.,Wolters, D.,Alexandrov, K. (deposition date: 2008-10-09, release date: 2009-07-07, Last modification date: 2023-11-01)

Primary citation

Nguyen, U.T.T.,Guo, Z.,Delon, C.,Wu, Y.,Deraeve, C.,Franzel, B.,Bon, R.S.,Blankenfeldt, W.,Goody, R.S.,Waldmann, H.,Wolters, D.,Alexandrov, K.
Analysis of the eukaryotic prenylome by isoprenoid affinity tagging
Nat.Chem.Biol., 5:227-235, 2009

PubMed Abstract: Protein prenylation is a widespread phenomenon in eukaryotic cells that affects many important signaling molecules. We describe the structure-guided design of engineered protein prenyltransferases and their universal synthetic substrate, biotin-geranylpyrophosphate. These new tools allowed us to detect femtomolar amounts of prenylatable proteins in cells and organs and to identify their cognate protein prenyltransferases. Using this approach, we analyzed the in vivo effects of protein prenyltransferase inhibitors. Whereas some of the inhibitors displayed the expected activities, others lacked in vivo activity or targeted a broader spectrum of prenyltransferases than previously believed. To quantitate the in vivo effect of the prenylation inhibitors, we profiled biotin-geranyl-tagged RabGTPases across the proteome by mass spectrometry. We also demonstrate that sites of active vesicular transport carry most of the RabGTPases. This approach enables a quantitative proteome-wide analysis of the regulation of protein prenylation and its modulation by therapeutic agents.

PubMed: 19219049
DOI: 10.1038/nchembio.149

Experimental method

X-RAY DIFFRACTION (2.8 Å)