Biomaterial Database

Structural characterization of the novel aminoglycoside phosphotransferase AphVIII from Streptomyces rimosus with enzymatic activity modulated by phosphorylation. 2016

Konstantin M Boyko, and Marina A Gorbacheva, and Dmitry A Korzhenevskiy, and Maria G Alekseeva, and Dilara A Mavletova, and Natalia V Zakharevich, and Sergey M Elizarov, and Natalia N Rudakova, and Valery N Danilenko, and Vladimir O Popov

Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow, Russian Federation; National Research Center "Kurchatov Institute", Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182, Russian Federation. Electronic address: kmb@inbi.ras.ru.

Aminoglycoside phosphotransferases represent a broad class of enzymes that promote bacterial resistance to aminoglycoside antibiotics via the phosphorylation of hydroxyl groups in the latter. Here we report the spatial structure of the 3'-aminoglycoside phosphotransferase of novel VIII class (AphVIII) solved by X-ray diffraction method with a resolution of 2.15 Å. Deep analysis of APHVIII structure and its comparison with known structures of aminoglycoside phosphotransferases of various types reveals that AphVIII has a typical two-domain fold and, however, possesses some unique characteristics that distinguish the enzyme from its known homologues. The most important difference is the presence of the activation loop with unique Ser146 residue. We demonstrate that in the apo-state of the enzyme the activation loop does not interact with other parts of the enzyme and seems to adopt catalytically competent state only after substrate binding.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D009711	Nucleotides	The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)	Nucleotide
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D018360	Crystallography, X-Ray	The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D019868	Kanamycin Kinase	A class of enzymes that inactivate aminocyclitol-aminoglycoside antibiotics (AMINOGLYCOSIDES) by regiospecific PHOSPHORYLATION of the 3' and/or 5' hydroxyl.	Aminoglycoside Phosphotransferase,Neomycin Phosphotransferase,APH(3')-IIIa,APH(3')-IIb,APHVII,APT-3'-I and II,Amikacin 3'-Phosphotransferase,Aminocyclitol Phosphotransferase,Aminoglycoside 3'-Phosphotransferase Type VIII,Aminoglycoside 3'-Phosphotransferases (I and II),Aminoglycoside Phosphotransferase Type III,Kanamycin-Neomycin Phosphate Transferase,Neomycin Phosphotransferase II,aphVII Gene Product,3'-Phosphotransferase, Amikacin,APT 3' I and II,Amikacin 3' Phosphotransferase,Aminoglycoside 3' Phosphotransferase Type VIII,Kanamycin Neomycin Phosphate Transferase,Kinase, Kanamycin,Phosphate Transferase, Kanamycin-Neomycin,Phosphotransferase II, Neomycin,Phosphotransferase, Aminocyclitol,Phosphotransferase, Aminoglycoside,Phosphotransferase, Neomycin,Transferase, Kanamycin-Neomycin Phosphate
D064411	Streptomyces rimosus	An actinomycete best known as the producer of the commercially important antibiotic OXYTETRACYCLINE.