4JX9

Crystal structure of the complex of peptidyl t-RNA hydrolase from Acinetobacter baumannii with uridine at 1.4A resolution

Summary for 4JX9

• Entry DOI: 10.2210/pdb4jx9/pdb
• Related: 4FOP 4FOT 4HOY 4IKO 4JWK 4JY7
• Descriptor: Peptidyl-tRNA hydrolase, URIDINE (3 entities in total)
• Functional Keywords: protein synthesis, complex, hydrolase
• Biological source: Acinetobacter baumannii ATCC 19606 = CIP 70.34
• Cellular location: Cytoplasm (By similarity): D0C9L6
• Total number of polymer chains: 1
• Total formula weight: 21212.16

Authors

Kaushik, S.,Singh, N.,Yamini, S.,Singh, A.,Sinha, M.,Kaur, P.,Sharma, S.,Singh, T.P. (deposition date: 2013-03-28, release date: 2013-06-05, Last modification date: 2023-11-08)

Primary citation

Kaushik, S.,Singh, N.,Yamini, S.,Singh, A.,Sinha, M.,Arora, A.,Kaur, P.,Sharma, S.,Singh, T.P.
The Mode of Inhibitor Binding to Peptidyl-tRNA Hydrolase: Binding Studies and Structure Determination of Unbound and Bound Peptidyl-tRNA Hydrolase from Acinetobacter baumannii
Plos One, 8:e67547-e67547, 2013

PubMed Abstract: The incidences of infections caused by an aerobic Gram-negative bacterium, Acinetobacter baumannii are very common in hospital environments. It usually causes soft tissue infections including urinary tract infections and pneumonia. It is difficult to treat due to acquired resistance to available antibiotics is well known. In order to design specific inhibitors against one of the important enzymes, peptidyl-tRNA hydrolase from Acinetobacter baumannii, we have determined its three-dimensional structure. Peptidyl-tRNA hydrolase (AbPth) is involved in recycling of peptidyl-tRNAs which are produced in the cell as a result of premature termination of translation process. We have also determined the structures of two complexes of AbPth with cytidine and uridine. AbPth was cloned, expressed and crystallized in unbound and in two bound states with cytidine and uridine. The binding studies carried out using fluorescence spectroscopic and surface plasmon resonance techniques revealed that both cytidine and uridine bound to AbPth at nanomolar concentrations. The structure determinations of the complexes revealed that both ligands were located in the active site cleft of AbPth. The introduction of ligands to AbPth caused a significant widening of the entrance gate to the active site region and in the process of binding, it expelled several water molecules from the active site. As a result of interactions with protein atoms, the ligands caused conformational changes in several residues to attain the induced tight fittings. Such a binding capability of this protein makes it a versatile molecule for hydrolysis of peptidyl-tRNAs having variable peptide sequences. These are the first studies that revealed the mode of inhibitor binding in Peptidyl-tRNA hydrolases which will facilitate the structure based ligand design.

PubMed: 23844024
DOI: 10.1371/journal.pone.0067547

Experimental method

X-RAY DIFFRACTION (1.4 Å)