4FE2

X-Ray Structure of SAICAR Synthetase (PurC) from Streptococcus pneumoniae complexed with AIR, ADP, Asp and Mg2+

Summary for 4FE2

• Entry DOI: 10.2210/pdb4fe2/pdb
• Descriptor: Phosphoribosylaminoimidazole-succinocarboxamide synthase, 5-AMINOIMIDAZOLE RIBONUCLEOTIDE, ADENOSINE-5'-DIPHOSPHATE, ... (9 entities in total)
• Functional Keywords: alpha/beta protein, saicar synthetase, cair, asp, ligase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 60625.67

Authors

Wolf, N.,Abad-Zapatero, C.,Johnson, M.E.,Fung, L.M.-W. (deposition date: 2012-05-29, release date: 2013-05-29, Last modification date: 2023-09-13)

Primary citation

Wolf, N.M.,Abad-Zapatero, C.,Johnson, M.E.,Fung, L.W.
Structures of SAICAR synthetase (PurC) from Streptococcus pneumoniae with ADP, Mg(2+), AIR and Asp.
Acta Crystallogr.,Sect.D, 70:841-850, 2014

PubMed Abstract: Streptococcus pneumoniae is a multidrug-resistant pathogen that is a target of considerable interest for antibacterial drug development. One strategy for drug discovery is to inhibit an essential metabolic enzyme. The seventh step of the de novo purine-biosynthesis pathway converts carboxyaminoimidazoleribonucleotide (CAIR) and L-aspartic acid (Asp) to 4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR) in the presence of adenosine 5'-triphosphate (ATP) using the enzyme PurC. PurC has been shown to be conditionally essential for bacterial replication. Two crystal structures of this essential enzyme from Streptococcus pneumoniae (spPurC) in the presence of adenosine 5'-diphosphate (ADP), Mg(2+), aminoimidazoleribonucleotide (AIR) and/or Asp have been obtained. This is the first structural study of spPurC, as well as the first of PurC from any species with Asp in the active site. Based on these findings, two model structures are proposed for the active site with all of the essential ligands (ATP, Mg(2+), Asp and CAIR) present, and a relay mechanism for the formation of the product SAICAR is suggested.

PubMed: 24598753
DOI: 10.1107/S139900471303366X

Experimental method

X-RAY DIFFRACTION (2.288 Å)