7NAA

Crystal structure of Mycobacterium tuberculosis H37Rv PknF kinase domain

Summary for 7NAA

• Entry DOI: 10.2210/pdb7naa/pdb
• Descriptor: Non-specific serine/threonine protein kinase, (4-{[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino}phenyl)[4-(pyrrolidin-1-yl)piperidin-1-yl]methanone (3 entities in total)
• Functional Keywords: pknf, mtb, transferase, structural genomics, psi-biology, protein structure initiative, structural genomics consortium, sgc, antimicrobial protein
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 4
• Total formula weight: 123419.64

Authors

Oliveira, A.A.,Cabarca, S.,dos Reis, C.V.,Takarada, J.E.,Counago, R.M.,Balan, A.,Structural Genomics Consortium (SGC) (deposition date: 2021-06-21, release date: 2021-08-04, Last modification date: 2023-10-18)

Primary citation

Cabarca, S.,Frazao de Souza, M.,Albert de Oliveira, A.,Vignoli Muniz, G.S.,Lamy, M.T.,Vinicius Dos Reis, C.,Takarada, J.,Effer, B.,Souza, L.S.,Iriarte de la Torre, L.,Counago, R.,Pinto Oliveira, C.L.,Balan, A.
Structure of the Mycobacterium tuberculosis c PknF and conformational changes induced in forkhead-associated regulatory domains.
Curr Res Struct Biol, 3:165-178, 2021

PubMed Abstract: () has 11 Serine-Threonine Protein Kinases (STPK) that control numerous physiological processes, including cell growth, cell division, metabolic flow, and transcription. PknF is one of the 11 Mtb STPKs that has, among other substrates, two FHA domains (FHA-1 and FHA-2) of the ATP-Binding Cassette (ABC) transporter Rv1747. Phosphorylation in T152 and T210 located in a non-structured linker that connects Rv1747 FHA domains is considerate to be the regulatory mechanism of the transporter. In this work, we resolved the three-dimensional structure of the PknF catalytic domain (cPknF) in complex with the human kinase inhibitor IKK16. cPknF is conserved when compared to other STPKs but shows specific residues in the binding site where the inhibitor is positioned. In addition, using Small Angle X-Ray Scattering analysis we monitored the behavior of the wild type and three FHA-phosphomimetic mutants in solution, and measured the cPknF affinity for these domains. The kinase showed higher affinity for the non-phosphorylated wild type domain and preference for phosphorylation of T152 inducing the rapprochement of the domains and significant structural changes. The results shed some light on the process of regulating the transporter's activity by phosphorylation and arises important questions about evolution and importance of this mechanism for the bacillus.

PubMed: 34382010
DOI: 10.1016/j.crstbi.2021.07.001

Experimental method

X-RAY DIFFRACTION (2.75 Å)