Protein flexibility and metal coordination changes in DHAP-dependent aldolases.
The mobility of rhamnulose-1-phosphate aldolase (RhuA) was analysed with a normal mode description and high level calculations on models of the active site. We report the connection between the mobility and the chemical properties of the active site, and compare them to a closely related enzyme, fuculose-1-phosphate aldolase (FucA). Calculations show that the different coordination number for the zinc ion, reported in the crystal structures of RhuA and FucA, was due to a different spatial arrangement of the residues, not to their different chemical nature. Moreover, the metal coordination change is correlated with activity. The domain mobility of the enzyme can reshape the active site of RhuA into the arrangement found in the FucA structure, and vice-versa. This has a direct influence on the energy barrier for the aldol reaction catalyzed by these enzymes, thus showing a coupling of the domain movements and the catalytic effects. Hence domain movements and the coordination chemistry of the active site metal suggest an explanation of why these enzymes have similar experimental turnover rates.
Jiménez
Aurora
A
Institut de Química Avançada de Catalunya IQAC-CSIC c/Jordi Girona 18-26, 08034, Barcelona, Catalonia, Spain.
Clapés
Pere
P
Crehuet
Ramon
R
D000446:Aldehyde-Lyases / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004099:Dihydroxyacetone Phosphate / Q000378:metabolism; D008956:Models, Chemical; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D014867:Water; D004099:Dihydroxyacetone Phosphate; D000446:Aldehyde-Lyases; C036027:L-fuculosephosphate aldolase; C022526:rhamnulose-1-phosphate adolase; D015032:Zinc