4DPL

Structure of malonyl-coenzyme A reductase from crenarchaeota in complex with NadP

Summary for 4DPL

• Entry DOI: 10.2210/pdb4dpl/pdb
• Related: 4DPK 4DPM
• Descriptor: Malonyl-CoA/succinyl-CoA reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, UNKNOWN LIGAND, ... (4 entities in total)
• Functional Keywords: dinucleotide binding, dimerization domain, reductase, nadp, coa, oxidoreductase
• Biological source: Sulfolobus tokodaii
• Total number of polymer chains: 4
• Total formula weight: 161412.53

Authors

Demmer, U.,Warkentin, E.,Srivastava, A.,Kockelkorn, D.,Fuchs, G.,Ermler, U. (deposition date: 2012-02-13, release date: 2013-01-16, Last modification date: 2024-10-30)

Primary citation

Demmer, U.,Warkentin, E.,Srivastava, A.,Kockelkorn, D.,Potter, M.,Marx, A.,Fuchs, G.,Ermler, U.
Structural Basis for a Bispecific NADP+ and CoA Binding Site in an Archaeal Malonyl-Coenzyme A Reductase.
J.Biol.Chem., 288:6363-6370, 2013

PubMed Abstract: Autotrophic members of the Sulfolobales (crenarchaeota) use the 3-hydroxypropionate/4-hydroxybutyrate cycle to assimilate CO2 into cell material. The product of the initial acetyl-CoA carboxylation with CO2, malonyl-CoA, is further reduced to malonic semialdehyde by an NADPH-dependent malonyl-CoA reductase (MCR); the enzyme also catalyzes the reduction of succinyl-CoA to succinic semialdehyde onwards in the cycle. Here, we present the crystal structure of Sulfolobus tokodaii malonyl-CoA reductase in the substrate-free state and in complex with NADP(+) and CoA. Structural analysis revealed an unexpected reaction cycle in which NADP(+) and CoA successively occupy identical binding sites. Both coenzymes are pressed into an S-shaped, nearly superimposable structure imposed by a fixed and preformed binding site. The template-governed cofactor shaping implicates the same binding site for the 3'- and 2'-ribose phosphate group of CoA and NADP(+), respectively, but a different one for the common ADP part: the β-phosphate of CoA aligns with the α-phosphate of NADP(+). Evolution from an NADP(+) to a bispecific NADP(+) and CoA binding site involves many amino acid exchanges within a complex process by which constraints of the CoA structure also influence NADP(+) binding. Based on the paralogous aspartate-β-semialdehyde dehydrogenase structurally characterized with a covalent Cys-aspartyl adduct, a malonyl/succinyl group can be reliably modeled into MCR and discussed regarding its binding mode, the malonyl/succinyl specificity, and the catalyzed reaction. The modified polypeptide surrounding around the absent ammonium group in malonate/succinate compared with aspartate provides the structural basis for engineering a methylmalonyl-CoA reductase applied for biotechnical polyester building block synthesis.

PubMed: 23325803
DOI: 10.1074/jbc.M112.421263

Experimental method

X-RAY DIFFRACTION (1.9 Å)