HUG Domain Is Responsible for Active Dimer Stabilization in an NrdJd Ribonucleotide Reductase

Fietze, TobiasChair of Molecular Biotechnology, Technische Universität Dresden, Dresden, Germany (författare)

Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to the corresponding deoxyribonucleotides. The catalytic activity of most RNRs depends on the formation of a dimer of the catalytic subunits. The active site is located at the interface, and part of the substrate binding site and regulatory mechanisms work across the subunit in the dimer. In this study, we describe and characterize a novel domain responsible for forming the catalytic dimer in several class II RNRs. The 3D structure of the class II RNR from Rhodobacter sphaeroides reveals a so far undescribed α-helical domain in the dimer interface, which is embracing the other subunit. Genetic removal of this HUG domain leads to a severe reduction of activity paired with reduced dimerization capability. In comparison with other described RNRs, the enzyme with this domain is less dependent on the presence of nucleotides to act as allosteric effectors in the formation of dimers. The HUG domain appears to serve as an interlock to keep the dimer intact and functional even at low enzyme and/or effector concentrations.

Wilk, PiotrMacromolecular Crystallography, Helmholtz-Zentrum Berlin, Berlin, Germany; Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland (författare)
Kabinger, FlorianDepartment of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen 37077, Germany (författare)
Anoosheh, SaberUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)saan0247 (författare)
Hofer, AndersUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)anho0002 (författare)
Lundin, Daniel,1965-Stockholms universitet,Institutionen för biokemi och biofysik,Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden(Swepub:su)dlund (författare)
Feiler, Christian G.Macromolecular Crystallography, Helmholtz-Zentrum Berlin, Berlin, Germany (författare)
Weiss, Manfred S.Macromolecular Crystallography, Helmholtz-Zentrum Berlin, Berlin, Germany (författare)
Loderer, ChristophChair of Molecular Biotechnology, Technische Universität Dresden, Dresden, Germany (författare)
Chair of Molecular Biotechnology, Technische Universität Dresden, Dresden, GermanyMacromolecular Crystallography, Helmholtz-Zentrum Berlin, Berlin, Germany; Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland (creator_code:org_t)

Ingår i:Biochemistry: American Chemical Society (ACS)61:15, s. 1633-16410006-29601520-4995

Av författaren/redakt...: Fietze, Tobias; Wilk, Piotr; Kabinger, Floria ...; Anoosheh, Saber; Hofer, Anders; Lundin, Daniel, ...; visa fler...; Feiler, Christia ...; Weiss, Manfred S ...; Loderer, Christo ...; visa färre...

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