Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Deciphering the allosteric regulation of mycobacterial inosine-5'-monophosphate dehydrogenase.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 6673, Year 2024
Publish date	Aug 6, 2024
Authors	Ondřej Bulvas / Zdeněk Knejzlík / Jakub Sýs / Anatolij Filimoněnko / Monika Čížková / Kamila Clarová / Dominik Rejman / Tomáš Kouba / Iva Pichová /
PubMed Abstract	Allosteric regulation of inosine 5'-monophosphate dehydrogenase (IMPDH), an essential enzyme of purine metabolism, contributes to the homeostasis of adenine and guanine nucleotides. However, the ...Allosteric regulation of inosine 5'-monophosphate dehydrogenase (IMPDH), an essential enzyme of purine metabolism, contributes to the homeostasis of adenine and guanine nucleotides. However, the precise molecular mechanism of IMPDH regulation in bacteria remains unclear. Using biochemical and cryo-EM approaches, we reveal the intricate molecular mechanism of the IMPDH allosteric regulation in mycobacteria. The enzyme is inhibited by both GTP and (p)ppGpp, which bind to the regulatory CBS domains and, via interactions with basic residues in hinge regions, lock the catalytic core domains in a compressed conformation. This results in occlusion of inosine monophosphate (IMP) substrate binding to the active site and, ultimately, inhibition of the enzyme. The GTP and (p)ppGpp allosteric effectors bind to their dedicated sites but stabilize the compressed octamer by a common mechanism. Inhibition is relieved by the competitive displacement of GTP or (p)ppGpp by ATP allowing IMP-induced enzyme expansion. The structural knowledge and mechanistic understanding presented here open up new possibilities for the development of allosteric inhibitors with antibacterial potential.
External links	Nat Commun / PubMed:39107302 / PubMed Central
Methods	EM (single particle)
Resolution	2.35 - 3.27 Å
Structure data	17988 8pw3 EMDB-17988, PDB-8pw3: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) apo form Method: EM (single particle) / Resolution: 2.507 Å 18184 8q65 EMDB-18184, PDB-8q65: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP-bound form Method: EM (single particle) / Resolution: 2.54 Å 18600 8qqp EMDB-18600: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+GTP-bound form, compressed PDB-8qqp: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+GTP-bound form, super-compressed Method: EM (single particle) / Resolution: 2.35 Å 18601 8qqq EMDB-18601: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+GTP-bound form, less-compressed PDB-8qqq: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+GTP-bound form, compressed Method: EM (single particle) / Resolution: 2.43 Å 18602 8qqr EMDB-18602: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+ppGpp-bound form, compressed PDB-8qqr: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+ppGpp-bound form, super-compressed Method: EM (single particle) / Resolution: 2.73 Å 18604 8qqt EMDB-18604: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+ppGpp-bound form, less-compressed PDB-8qqt: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+ppGpp-bound form, compressed Method: EM (single particle) / Resolution: 2.76 Å 18606 8qqv EMDB-18606, PDB-8qqv: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+IMP-bound form, extended Method: EM (single particle) / Resolution: 2.99 Å 18607 8qqw EMDB-18607, PDB-8qqw: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP-bound form, compressed Method: EM (single particle) / Resolution: 3.27 Å 18608 8qqx EMDB-18608, PDB-8qqx: Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) ATP+IMP-bound form, half-extended Method: EM (single particle) / Resolution: 3.01 Å
Chemicals	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM ChemComp-HOH: WATER ChemComp-G4P: GUANOSINE-5',3'-TETRAPHOSPHATE ChemComp-IMP: INOSINIC ACID
Source	mycolicibacterium smegmatis mc2 155 (bacteria)
Keywords	OXIDOREDUCTASE / Octamer / Apo enzyme / Purine metabolism / IMPDH / ATP-bound complex / ATP+GTP complex / ATP+ppGpp complex / ATP+IMP complex / ATP complex