Precursors of inosine 5′-monophosphate. R5P is ribose 5′-phosphate.

The purine biosynthetic pathway. Steps 1–10 define the original pathway worked out by Buchanan. Steps 3a, 4a, 6a, 6b, 9a and 10a represent variations of the pathway found in other organisms.

The proposed acylphosphate intermediate in the reactions catalyzed by PurD, PurK, PurT and PurP. Nu: for PurD is the amino group of PRA, for PurK, the 5-amino group of AIR, for PurT, the amino group of GAR and for PurP, the amino group of AICAR. R5P is ribose 5′-phosphate. The amide group formed in each reaction is indicated by a dashed box.

Structures of PurF (step 1), PurD (step 2), PurN (step 3) and PurT (step 3a). (A) Ribbon diagram of the E. coli PurF (PDB: 1ECB) tetramer. Each monomer is in a different color, and the inhibitor, GMP, is in ball-and-stick representation, colored by atom type (with carbon black, oxygen red, nitrogen blue, sulfur yellow, and phosphorus orange, throughout). (B) Ribbon diagram of a monomer of E. coli PurF (PDB: 1ECC), color-coded by secondary structure. Ligands, Gln and cPRPP, bound in the active sites are in ball-and-stick representation. (C) Ribbon diagram of Geobacillus kaustophilus PurD (PDB: 2YS6), color-coded by secondary structure. Glycine and AMP, found in the active site, are in ball-and-stick representation. (D) Ribbon diagram of E. coli PurN (PDB: 1CDE), color-coded by secondary structure. The substrate glycinamide ribonucleotide and the inhibitor 5-deaza-5,6,7,8-tetrahydrafolate are in ball-and-stick representation. (E) Ribbon diagram of the E. coli PurT dimer (PDB: 1KJ8), color coded by monomer. The substrate, glycinamide ribonucleotide (GAR), and ATP are shown in ball-and-stick representation. (F) Ribbon diagram of the E. coli PurT monomer, color-coded by secondary structure. GAR and ATP are shown in ball-and-stick representation.

Active sites of PurF. (A) Schematic diagram of the active site residues and the covalently bound ligand, Gln, in the PurF glutaminase domain. Dashed lines represent hydrogen bonds. (B) Schematic representation of the active site residues and the bound ligand, cPRPP, in the PurF phosphoribosyl transferase domain.

Active site of PurD. Schematic diagram of the active site residues and ligands, AMP and glycine. Dashed lines represent hydrogen bonds.

Active site of PurN. Schematic diagram of the active site residues, substrate GAR (A) and inhibitor, 5-deazatetrahydrfolate (B). Dashed lines represent hydrogen bonds.

Active site of PurT. Schematic diagram of the active site residues, GAR and ATP. Hydrogen bonds are indicated by dashed lines, except for those between the phosphate groups of ATP and Gln165, Arg114 and the P-loop, which are omitted for clarity.

Structures of PurL (step 4), PurM (step 5) and PurK (step 6a). (A) Ribbon diagram of the large PurL structure from S. typhimurium (PDB: 1T3T) color-coded by secondary structure. Ligands, Gln and ADP, are in ball-and-stick representation. (B) Ribbon diagram of the PurLQS complex structure from T. maritima (PDB: 3D54), each monomer in the complex is in a different color. Ligands, Gln and ADP, are in ball-and-stick representation. (C) Ribbon diagrams of PurL, PurQ and PurS monomers from T. maritima, individually, color-coded by secondary structure. Ligands are in ball-and-stick representation. Ligands bound in the active of PurL are FGAR and AMPPCP (PDB: 2HS4), and the ligand in the auxiliary site is ATP (PDB: 2HS0). The ligand in PurQ is Gln. (D) Ribbon diagram of the PurM dimer from E. coli (PDB: 1CLI) color coded by monomer. (E) Ribbon diagram of the monomer of PurM, color-coded by secondary structure. (F) Ribbon diagram of the E. coli PurK dimer (PDB: 1B6S), color coded by monomer and with ADP in ball-and-stick representation. (G) Ribbon diagram of the PurK monomer, color-coded by secondary structure and with ADP in ball-and-stick representation.

Active site of PurL. (A) Schematic diagram of the PurL active site showing the ligands, FGAR and AMPPCP, and the residues interacting with the ligands. (B) Schematic diagram of the PurQ active site showing the covalently bound ligand, Gln, and the residues interacting with the ligand. Dashed lines represent hydrogen bonds.

The proposed iminophosphate intermediate in reactions catalyzed by PurL and PurM. R5P is ribose 5′-phosphate. The amidine formed in each reaction is highlighted by a dashed circle.

Active site of PurK. Schematic diagram of the active site residues and ADP. Dashed lines represent hydrogen bonds.

Structures of class I PurE (Step 6b), PurCE (Steps 6 and 7), PurC (Step 7) and PurB (Step 8). (A) Ribbon diagram of the E. coli PurE octamer (PDB: 2ATE) with the eight monomers shown in different colors. 4-Nitroaminoimidazole ribonucleotide (nitroAIR), an analog of the product carboxyaminoimidazole ribonucleotide (CAIR), is shown in ball-and-stick representation. (B) Ribbon diagram of the PurE monomer, color-coded by secondary structure and with nitroAIR shown in ball-and-stick representation. (C) The ribbon diagram of bifunctional human PurCE (PDB: 2H31). The octameric PurE core is in yellow, decorated with four PurC dimers in red. (D) Ribbon diagram of the E. coli PurC dimer (PDB: 2GQS) color coded by monomer. The substrate carboxyaminoimidazole ribonucleotide (CAIR) and associated ADP are shown in ball-and-stick representation. (E) Ribbon diagram of the PurC monomer color coded by secondary structure and with CAIR and ADP shown in ball-and-stick representation. (F) Ribbon diagram of the E. coli PurB tetramer (PDB: 2PTR) color-coded by monomer. PurB also catalyzes the second and final step in the conversion of IMP to AMP. The ligand adenylosuccinate bound at each active site is shown in ball-and-stick representation. (G) A monomer of PurB color-coded by secondary structure and with the ligand adenylosuccinate shown in ball-and-stick representation.

Active site of Class I PurE. Schematic diagram of the active site residues associated with nitroAIR. Dashed lines represent hydrogen bonds.

Active site of PurC. Schematic diagram of the active site residues associated with ADP and CAIR. Dashed lines represent hydrogen bonds.

Active Site of PurB. The chain id for each residue is given in parentheses. Hydrogen bonds are indicated by dashed lines. Proposed catalytic residues are highlighted by rectangular frames.

Structures of PurHJ (Steps 9 and 10), PurP (Steps 9a) and PurO (Step 10a). (A) Ribbon diagram of human PurHJ (PDB: 1P4R) color-coded by monomers. Ligands AICAR, folate-based inhibitor, and XMP are shown in ball-and-stick representation. (B) The PurH domain colored by secondary structure elements. Ligands AICAR and folate-based inhibitor are shown in ball-and-stick representation. The N-terminus connecting to the PurJ domain is indicated by the asterisk. (C) The PurJ domain colored by secondary structural elements. The asterisk indicates the C-terminus connecting to the PurJ domain. The substrate analog XMP is shown in ball-and-stick representation. (D) The hexamer of M. jannaschii PurP (PDB: 2R7L) colored by monomer and viewed down the 3-fold symmetry. (E) Ribbon diagram of a monomer of PurP colored by secondary structural elements. ATP and AICAR are shown in ball-and-stick representation. (F) Ribbon diagram of the M. thermoautotrophicus PurO tetramer (PDB: 2NTK). The diagram is colored by monomer, with IMP shown in ball-and-stick representation at each active site. (G) A PurO monomer colored by secondary structural elements, with IMP shown in ball-and-stick representation.

Active sites of PurH and PurJ. (A) Schematic diagram of the PurH active site formed at the dimer interface. Letters in parenthesis refer to the chain id for each residue. Hydrogen bonds are indicated by dashed lines. (B) Schematic diagram of the PurJ active site with XMP bound.

Active site of PurP. The active site of PurP is shown in schematic diagram, with hydrogen bonds indicated by dashed lines. The active site is comprised of residues from three adjacent monomers. The chain id for each residue is indicated in parenthesis.

Active site of PurO. The schematic diagram shows bound IMP. Hydrogen bonds to IMP are indicated by dashed lines.