4FUT

Crystal structure of ATP bound MatB from Rhodopseudomonas palustris

Summary for 4FUT

• Entry DOI: 10.2210/pdb4fut/pdb
• Related: 3NYQ 3NYR
• Descriptor: Malonyl CoA synthetase, GLYCEROL, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: anl superfamily, methymalonyl-coa synthetase, coa, methylmalonate, malonate, ligase
• Biological source: Rhodopseudomonas palustris
• Total number of polymer chains: 1
• Total formula weight: 56305.32

Authors

Rank, K.C.,Crosby, H.A.,Escalante-Semerena, J.C.,Rayment, I. (deposition date: 2012-06-28, release date: 2012-07-25, Last modification date: 2024-04-03)

Primary citation

Crosby, H.A.,Rank, K.C.,Rayment, I.,Escalante-Semerena, J.C.
Structure-Guided Expansion of the Substrate Range of Methylmalonyl Coenzyme A Synthetase (MatB) of Rhodopseudomonas palustris.
Appl.Environ.Microbiol., 78:6619-6629, 2012

PubMed Abstract: Malonyl coenzyme A (malonyl-CoA) and methylmalonyl-CoA are two of the most commonly used extender units for polyketide biosynthesis and are utilized to synthesize a vast array of pharmaceutically relevant products with antibacterial, antiparasitic, anticholesterol, anticancer, antifungal, and immunosuppressive properties. Heterologous hosts used for polyketide production such as Escherichia coli often do not produce significant amounts of methylmalonyl-CoA, however, requiring the introduction of other pathways for the generation of this important building block. Recently, the bacterial malonyl-CoA synthetase class of enzymes has been utilized to generate malonyl-CoA and methylmalonyl-CoA directly from malonate and methylmalonate. We demonstrate that in the purple photosynthetic bacterium Rhodopseudomonas palustris, MatB (RpMatB) acts as a methylmalonyl-CoA synthetase and is required for growth on methylmalonate. We report the apo (1.7-Å resolution) and ATP-bound (2.0-Å resolution) structure and kinetic analysis of RpMatB, which shows similar activities for both malonate and methylmalonate, making it an ideal enzyme for heterologous polyketide biosynthesis. Additionally, rational, structure-based mutagenesis of the active site of RpMatB led to substantially higher activity with ethylmalonate and butylmalonate, demonstrating that this enzyme is a prime target for expanded substrate specificity.

PubMed: 22773649
DOI: 10.1128/AEM.01733-12

Experimental method

X-RAY DIFFRACTION (2 Å)