2NM3

Crystal structure of dihydroneopterin aldolase from S. aureus in complex with (1S,2S)-monapterin at 1.68 angstrom resolution

Summary for 2NM3

• Entry DOI: 10.2210/pdb2nm3/pdb
• Related: 1DHN 1NBU 1RR5 1RRI 1RRW 1RRY 1RS2 1RS4 1RSD 1RSI 2DHN 2NM2
• Descriptor: Dihydroneopterin aldolase, ACETATE ION, D-MONAPTERIN, ... (4 entities in total)
• Functional Keywords: dihydroneopterin aldolase, dhna, substrate complex, monapterin, neopterin, 7, 8-dihydromonapterin, drug design, lyase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 14081.89

Authors

Blaszczyk, J.,Ji, X.,Yan, H. (deposition date: 2006-10-20, release date: 2007-09-04, Last modification date: 2023-08-30)

Primary citation

Blaszczyk, J.,Li, Y.,Gan, J.,Yan, H.,Ji, X.
Structural basis for the aldolase and epimerase activities of Staphylococcus aureus dihydroneopterin aldolase.
J.Mol.Biol., 368:161-169, 2007

PubMed Abstract: Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) and the epimerization of DHNP to 7,8-dihydromonopterin (DHMP). Although crystal structures of the enzyme from several microorganisms have been reported, no structural information is available about the critical interactions between DHNA and the trihydroxypropyl moiety of the substrate, which undergoes bond cleavage and formation. Here, we present the structures of Staphylococcus aureus DHNA (SaDHNA) in complex with neopterin (NP, an analog of DHNP) and with monapterin (MP, an analog of DHMP), filling the gap in the structural analysis of the enzyme. In combination with previously reported SaDHNA structures in its ligand-free form (PDB entry 1DHN) and in complex with HP (PDB entry 2DHN), four snapshots for the catalytic center assembly along the reaction pathway can be derived, advancing our knowledge about the molecular mechanism of SaDHNA-catalyzed reactions. An additional step appears to be necessary for the epimerization of DHMP to DHNP. Three active site residues (E22, K100, and Y54) function coordinately during catalysis: together, they organize the catalytic center assembly, and individually, each plays a central role at different stages of the catalytic cycle.

PubMed: 17331536
DOI: 10.1016/j.jmb.2007.02.009

Experimental method

X-RAY DIFFRACTION (1.68 Å)