4RPA

Crystal structure of inorganic pyrophosphatase from Staphylococcus aureus in complex with Mn2+

Summary for 4RPA

• Entry DOI: 10.2210/pdb4rpa/pdb
• Descriptor: Probable manganese-dependent inorganic pyrophosphatase, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: mixed alpha/beta fold, inorganic pyrophosphatase, hydrolase
• Biological source: Staphylococcus aureus
• Cellular location: Cytoplasm : D9RMT1
• Total number of polymer chains: 2
• Total formula weight: 70701.51

Authors

Gajadeera, C.S.,Tsodikov, O.V. (deposition date: 2014-10-30, release date: 2015-01-21, Last modification date: 2023-12-06)

Primary citation

Gajadeera, C.S.,Zhang, X.,Wei, Y.,Tsodikov, O.V.
Structure of inorganic pyrophosphatase from Staphylococcus aureus reveals conformational flexibility of the active site.
J.Struct.Biol., 189:81-86, 2015

PubMed Abstract: Cytoplasmic inorganic pyrophosphatase (PPiase) is an enzyme essential for survival of organisms, from bacteria to human. PPiases are divided into two structurally distinct families: family I PPiases are Mg(2+)-dependent and present in most archaea, eukaryotes and prokaryotes, whereas the relatively less understood family II PPiases are Mn(2+)-dependent and present only in some archaea, bacteria and primitive eukaryotes. Staphylococcus aureus (SA), a dangerous pathogen and a frequent cause of hospital infections, contains a family II PPiase (PpaC), which is an attractive potential target for development of novel antibacterial agents. We determined a crystal structure of SA PpaC in complex with catalytic Mn(2+) at 2.1Å resolution. The active site contains two catalytic Mn(2+) binding sites, each half-occupied, reconciling the previously observed 1:1 Mn(2+):enzyme stoichiometry with the presence of two divalent metal ion sites in the apo-enzyme. Unexpectedly, despite the absence of the substrate or products in the active site, the two domains of SA PpaC form a closed active site, a conformation observed in structures of other family II PPiases only in complex with substrate or product mimics. A region spanning residues 295-298, which contains a conserved substrate binding RKK motif, is flipped out of the active site, an unprecedented conformation for a PPiase. Because the mutant of Arg295 to an alanine is devoid of activity, this loop likely undergoes an induced-fit conformational change upon substrate binding and product dissociation. This closed conformation of SA PPiase may serve as an attractive target for rational design of inhibitors of this enzyme.

PubMed: 25576794
DOI: 10.1016/j.jsb.2014.12.003

Experimental method

X-RAY DIFFRACTION (2.1 Å)