4DQW

Crystal Structure Analysis of PA3770

Summary for 4DQW

• Entry DOI: 10.2210/pdb4dqw/pdb
• Descriptor: Inosine-5'-monophosphate dehydrogenase, ADENOSINE-5'-TRIPHOSPHATE, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: impdh enzyme, oxidoreductase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 110312.94

Authors

Labesse, G.,Munier-Lehmann, H. (deposition date: 2012-02-16, release date: 2013-03-06, Last modification date: 2024-02-28)

Primary citation

Labesse, G.,Alexandre, T.,Vaupre, L.,Salard-Arnaud, I.,Him, J.L.,Raynal, B.,Bron, P.,Munier-Lehmann, H.
MgATP Regulates Allostery and Fiber Formation in IMPDHs.
Structure, 21:975-985, 2013

PubMed Abstract: Inosine-5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in nucleotide biosynthesis studied as an important therapeutic target and its complex functioning in vivo is still puzzling and debated. Here, we highlight the structural basis for the regulation of IMPDHs by MgATP. Our results demonstrate the essential role of the CBS tandem, conserved among almost all IMPDHs. We found that Pseudomonas aeruginosa IMPDH is an octameric enzyme allosterically regulated by MgATP and showed that this octameric organization is widely conserved in the crystal structures of other IMPDHs. We also demonstrated that human IMPDH1 adopts two types of complementary octamers that can pile up into isolated fibers in the presence of MgATP. The aggregation of such fibers in the autosomal dominant mutant, D226N, could explain the onset of the retinopathy adRP10. Thus, the regulatory CBS modules in IMPDHs are functional and they can either modulate catalysis or macromolecular assembly.

PubMed: 23643948
DOI: 10.1016/j.str.2013.03.011

Experimental method

X-RAY DIFFRACTION (2.51 Å)