2RKX

The 3D structure of chain D, cyclase subunit of imidazoleglycerol_evolvedcerolphosphate synthase

Summary for 2RKX

• Entry DOI: 10.2210/pdb2rkx/pdb
• Related: 1THF
• Descriptor: Cyclase subunit of imidazoleglycerol_evolvedcerolphosphate synthase (2 entities in total)
• Functional Keywords: alpha-beta barrel, structural genomics, israel structural proteomics center, ispc, amino-acid biosynthesis, cytoplasm, histidine biosynthesis, lyase
• Total number of polymer chains: 1
• Total formula weight: 28051.21

Authors

Tawfik, D.,Khersonsky, O.,Albeck, S.,Dym, O.,Israel Structural Proteomics Center (ISPC) (deposition date: 2007-10-18, release date: 2008-03-18, Last modification date: 2023-08-30)

Primary citation

Rothlisberger, D.,Khersonsky, O.,Wollacott, A.M.,Jiang, L.,DeChancie, J.,Betker, J.,Gallaher, J.L.,Althoff, E.A.,Zanghellini, A.,Dym, O.,Albeck, S.,Houk, K.N.,Tawfik, D.S.,Baker, D.
Kemp elimination catalysts by computational enzyme design.
Nature, 453:190-195, 2008

PubMed Abstract: The design of new enzymes for reactions not catalysed by naturally occurring biocatalysts is a challenge for protein engineering and is a critical test of our understanding of enzyme catalysis. Here we describe the computational design of eight enzymes that use two different catalytic motifs to catalyse the Kemp elimination-a model reaction for proton transfer from carbon-with measured rate enhancements of up to 10(5) and multiple turnovers. Mutational analysis confirms that catalysis depends on the computationally designed active sites, and a high-resolution crystal structure suggests that the designs have close to atomic accuracy. Application of in vitro evolution to enhance the computational designs produced a >200-fold increase in k(cat)/K(m) (k(cat)/K(m) of 2,600 M(-1)s(-1) and k(cat)/k(uncat) of >10(6)). These results demonstrate the power of combining computational protein design with directed evolution for creating new enzymes, and we anticipate the creation of a wide range of useful new catalysts in the future.

PubMed: 18354394
DOI: 10.1038/nature06879

Experimental method

X-RAY DIFFRACTION (2.25 Å)