4R5Z

Crystal structure of Rv3772 encoded aminotransferase

Summary for 4R5Z

• Entry DOI: 10.2210/pdb4r5z/pdb
• Descriptor: Putative phenylalanine aminotransferase, SUCCINIC ACID, 4'-DEOXY-4'-AMINOPYRIDOXAL-5'-PHOSPHATE, ... (6 entities in total)
• Functional Keywords: aminotransferase, transferase
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 4
• Total formula weight: 163077.06

Authors

Nasir, N.,Anant, A.,Vyas, R.,Biswal, B.K. (deposition date: 2014-08-22, release date: 2015-08-26, Last modification date: 2023-11-08)

Primary citation

Nasir, N.,Anant, A.,Vyas, R.,Biswal, B.K.
Crystal structures of Mycobacterium tuberculosis HspAT and ArAT reveal structural basis of their distinct substrate specificities
Sci Rep, 6:18880-18880, 2016

PubMed Abstract: Aminotransferases of subfamily Iβ, which include histidinol phosphate aminotransferases (HspATs) and aromatic amino acid aminotransferases (ArATs), are structurally similar but possess distinct substrate specificities. This study, encompassing structural and biochemical characterisation of HspAT and ArAT from Mycobacterium tuberculosis demonstrates that the residues lining the substrate binding pocket and N-terminal lid are the primary determinants of their substrate specificities. In mHspAT, hydrophilic residues in the substrate binding pocket and N-terminal lid allow the entry and binding of its preferential substrate, Hsp. On the other hand, the hydrophobic nature of both the substrate binding pocket and the N-terminal lid of mArAT is responsible for the discrimination of a polar substrate such as Hsp, while facilitating the binding of Phe and other aromatic residues such as Tyr and Trp. In addition, the present study delineates the ligand induced conformational rearrangements, providing insights into the plasticity of aminotransferases. Furthermore, the study also demonstrates that the adventitiously bound ligand 2-(N-morpholino)ethanesulfonic acid (MES) is indeed a specific inhibitor of HspAT. These results suggest that previously untapped morpholine-ring scaffold compounds could be explored for the design of new anti-TB agents.

PubMed: 26738801
DOI: 10.1038/srep18880

Experimental method

X-RAY DIFFRACTION (1.95 Å)