Summary for 3TYK
| Entry DOI | 10.2210/pdb3tyk/pdb |
| Descriptor | Hygromycin-B 4-O-kinase, HYGROMYCIN B VARIANT, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | midwest center for structural genomics, mcsg, psi-2, aminoglycoside phosphotransferase, eukaryotic protein kinase-like fold, phosphotransferase/kinase, antibiotic resistance, aminoglycoside binding, phosphorylation, transferase-antibiotic complex, cytoplasmic, protein structure initiative, transferase/antibiotic |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 41503.21 |
| Authors | Stogios, P.J.,Shabalin, I.G.,Shakya, T.,Evdokmova, E.,Fan, Y.,Chruszcz, M.,Minor, W.,Wright, G.D.,Savchenko, A.,Anderson, W.F.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2011-09-26, release date: 2011-10-12, Last modification date: 2022-04-13) |
| Primary citation | Stogios, P.J.,Shakya, T.,Evdokimova, E.,Savchenko, A.,Wright, G.D. Structure and function of APH(4)-Ia, a hygromycin B resistance enzyme. J.Biol.Chem., 286:1966-1975, 2011 Cited by PubMed Abstract: The aminoglycoside phosphotransferase (APH) APH(4)-Ia is one of two enzymes responsible for bacterial resistance to the atypical aminoglycoside antibiotic hygromycin B (hygB). The crystal structure of APH(4)-Ia enzyme was solved in complex with hygB at 1.95 Å resolution. The APH(4)-Ia structure adapts a general two-lobe architecture shared by other APH enzymes and eukaryotic kinases, with the active site located at the interdomain cavity. The enzyme forms an extended hydrogen bond network with hygB primarily through polar and acidic side chain groups. Individual alanine substitutions of seven residues involved in hygB binding did not have significant effect on APH(4)-Ia enzymatic activity, indicating that the binding affinity is spread across a distributed network. hygB appeared as the only substrate recognized by APH(4)-Ia among the panel of 14 aminoglycoside compounds. Analysis of the active site architecture and the interaction with the hygB molecule demonstrated several unique features supporting such restricted substrate specificity. Primarily the APH(4)-Ia substrate-binding site contains a cluster of hydrophobic residues that provides a complementary surface to the twisted structure of the substrate. Similar to APH(2″) enzymes, the APH(4)-Ia is able to utilize either ATP or GTP for phosphoryl transfer. The defined structural features of APH(4)-Ia interactions with hygB and the promiscuity in regard to ATP or GTP binding could be exploited for the design of novel aminoglycoside antibiotics or inhibitors of this enzyme. PubMed: 21084294PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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