5AHM

IMP-bound form of the DeltaCBS mutant of IMPDH from Pseudomonas aeruginosa

Summary for 5AHM

• Entry DOI: 10.2210/pdb5ahm/pdb
• Related: 5AHL 5AHN
• Descriptor: INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE, INOSINIC ACID, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: oxidoreductase, cbs module, deletion mutant, allosteric regu nucleotide metabolism
• Biological source: PSEUDOMONAS AERUGINOSA PAO1
• Total number of polymer chains: 2
• Total formula weight: 84576.41

Authors

Labesse, G.,Alexandre, T.,Gelin, M.,Haouz, A.,Munier-Lehmann, H. (deposition date: 2015-02-06, release date: 2015-07-15, Last modification date: 2024-01-10)

Primary citation

Labesse, G.,Alexandre, T.,Gelin, M.,Haouz, A.,Munier-Lehmann, H.
Crystallographic Studies of Two Variants of Pseudomonas Aeruginosa Impdh with Impaired Allosteric Regulation
Acta Crystallogr.,Sect.D, 71:1890-, 2015

PubMed Abstract: Inosine-5'-monophosphate dehydrogenases (IMPDHs), which are the rate-limiting enzymes in guanosine-nucleotide biosynthesis, are important therapeutic targets. Despite in-depth functional and structural characterizations of various IMPDHs, the role of the Bateman domain containing two CBS motifs remains controversial. Their involvement in the allosteric regulation of Pseudomonas aeruginosa IMPDH by Mg-ATP has recently been reported. To better understand the function of IMPDH and the importance of the CBS motifs, the structure of a variant devoid of these modules (ΔCBS) was solved at high resolution in the apo form and in complex with IMP. In addition, a single amino-acid substitution variant, D199N, was also structurally characterized: the mutation corresponds to the autosomal dominant mutant D226N of human IMPDH1, which is responsible for the onset of the retinopathy adRP10. These new structures shed light onto the possible mechanism of regulation of the IMPDH enzymatic activity. In particular, three conserved loops seem to be key players in this regulation as they connect the tetramer-tetramer interface with the active site and show significant modification upon substrate binding.

PubMed: 26327379
DOI: 10.1107/S1399004715013115

Experimental method

X-RAY DIFFRACTION (1.74 Å)