4BGF

The 3D-structure of arylamine-N-acetyltransferase from M. tuberculosis

Summary for 4BGF

• Entry DOI: 10.2210/pdb4bgf/pdb
• Descriptor: ARYLAMINE N-ACETYLTRANSFERASE NAT (2 entities in total)
• Functional Keywords: transferase, drug design, cross-seeding, micro-seeding, microseed matrix screen
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 8
• Total formula weight: 248504.95

Authors

Abuhammad, A.,Lowe, E.D.,McDonough, M.A.,Shaw Stewart, P.D.,Kolek, S.A.,Sim, E.,Garman, E.F. (deposition date: 2013-03-26, release date: 2013-07-24, Last modification date: 2023-12-20)

Primary citation

Abuhammad, A.,Lowe, E.D.,McDonough, M.A.,Shaw Stewart, P.D.,Kolek, S.A.,Sim, E.,Garman, E.F.
Structure of arylamine N-acetyltransferase from Mycobacterium tuberculosis determined by cross-seeding with the homologous protein from M. marinum: triumph over adversity.
Acta Crystallogr. D Biol. Crystallogr., 69:1433-1446, 2013

PubMed Abstract: Arylamine N-acetyltransferase from Mycobacterium tuberculosis (TBNAT) plays an important role in the intracellular survival of the microorganism inside macrophages. Medicinal chemistry efforts to optimize inhibitors of the TBNAT enzyme have been hampered by the lack of a three-dimensional structure of the enzyme. In this paper, the first structure of TBNAT, determined using a lone crystal produced using cross-seeding with the homologous protein from M. marinum, is reported. Despite the similarity between the two enzymes (74% sequence identity), they show distinct physical and biochemical characteristics. The structure elegantly reveals the characteristic features of the protein surface as well as details of the active site of TBNAT relevant to drug-discovery efforts. The crystallographic analysis of the diffraction data presented many challenges, since the crystal was twinned and the habit possessed pseudo-translational symmetry.

PubMed: 23897467
DOI: 10.1107/S0907444913015126

Experimental method

X-RAY DIFFRACTION (2.097 Å)