Altering Enzyme Substrate and Cofactor Specificity via Protein Engineering

DeSieno, Matthew A.; Du, Jing; Zhao, Huimin

doi:10.1002/9783527634026.ch31

Cited by 2 publications

(3 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After the identification of those amino acids ('hot spots') that could change the propriety of the enzyme by modelling software, the successive step is carrying out site-direct mutagenesis (SDM). 48 Several are the cases of the success of this technique. 48,[51][52][53] For example, Wang and co-workers changed the substrate specificity of methylamine dehydrogenase 54 ; Dang and co-workers altered the serine protease shifting the equilibrium between anticoagulant and procoagulant activities; 55 and Martí and co-workers improved the efficiency of the 1F7 CA, which catalyses the rearrangement of the chorismate to prephenate.…”

Section: Rational Designmentioning

confidence: 99%

“…48 Several are the cases of the success of this technique. 48,[51][52][53] For example, Wang and co-workers changed the substrate specificity of methylamine dehydrogenase 54 ; Dang and co-workers altered the serine protease shifting the equilibrium between anticoagulant and procoagulant activities; 55 and Martí and co-workers improved the efficiency of the 1F7 CA, which catalyses the rearrangement of the chorismate to prephenate. 56 It is interesting to note that in contrast to directed evolution, in rational design the mutations are focused on the region close to or inside the active site.…”

Section: Rational Designmentioning

confidence: 99%

“…Until a few years ago, the rational design was restricted to several well-studied systems, due to a partial comprehension of the structure-function relationship. 48 Nowadays, this methodology is becoming more accessible thanks to sequence information today available and a high number of protein structures deposited in the Brookhaven protein database (PDB). Additionally, a plethora of software that has been developed, increase the success rate of modelling predictions.…”

Section: Rational Designmentioning

confidence: 99%

See 2 more Smart Citations

Computational studies of the Retro-Aldol reaction catalyzed by different protein scaffolds. Towards the redesign of an improved enzyme

Raffele¹

View full text Add to dashboard Cite

Thanks to the lovely Merche, and then Kemel, Maite for their pleasant company during lunch (even if I will never get used to the Spanish lunchtime). Many thanks to Kasia, because I've learned a lot also from you. Thanks to Santiago with his mad humor (know that it was me who unplugged the screen and the keyboard… and yes, all the other stuff. Now I can tell you). Thanks to Ezequiel for the interesting discussions (I forgave you for saying that carbonara is made with cream). Finally, thanks to Juan, Monica, Sixte and particularly Silvia for the pleasant conversations.I must express my gratitude to my darling, Vincenzo, who always believed in me, encouraged me and provided stimulating discussions. You have motivated me to do my best. Thank you for your kindness and for being part of my story. Your support was wonderful! And let me finish in Italian the last acknowledgement: Ringrazio i miei genitori che sono il pilastro della mia vita, le fondamenta dei miei giorni. Questa tesi è per loro e a loro dedico la felicità di questo traguardo. Con gratitudine sconfinata.

show abstract

Section: Rational Designmentioning

confidence: 99%

Section: Rational Designmentioning

confidence: 99%

Section: Rational Designmentioning

confidence: 99%

See 1 more Smart Citation

Computational studies of the Retro-Aldol reaction catalyzed by different protein scaffolds. Towards the redesign of an improved enzyme

Raffele¹

View full text Add to dashboard Cite

show abstract

Recent advances in imine reductase-catalyzed reactions

Lenz

Borlinghaus

Weinmann

et al. 2017

World J Microbiol Biotechnol

View full text Add to dashboard Cite

Imine reductases are nicotinamide-dependent enzymes that catalyze the asymmetric reduction of various imines to the corresponding amine products. Owing to the increasing roles of chiral amines and heterocyclic compounds as intermediates for pharmaceuticals, the demand for novel selective synthesis strategies is vitally important. Recent studies have demonstrated the discovery and structural characterization of a number of stereoselective imine reductase enzymes. Here, we highlight recent progress in applying imine reductases for the formation of chiral amines and heterocycles. It particularly focuses on the utilization of imine reductases in reductive aminations of aldehydes and ketones with various amine nucleophiles, one of the most powerful reactions in the synthesis of chiral amines. Second, we report on the synthesis of saturated substituted N-heterocycles by combining them with further biocatalysts, such as carboxylic acid reductases, oxidases or transaminases. Finally, we summarize the latest applications of imine reductases in the promiscuous asymmetric hydrogenation of a highly reactive carbonyl compound and the engineering of the cofactor specificity from NADPH to NADH.

show abstract

Altering Enzyme Substrate and Cofactor Specificity via Protein Engineering

Cited by 2 publications

References 59 publications

Computational studies of the Retro-Aldol reaction catalyzed by different protein scaffolds. Towards the redesign of an improved enzyme

Computational studies of the Retro-Aldol reaction catalyzed by different protein scaffolds. Towards the redesign of an improved enzyme

Recent advances in imine reductase-catalyzed reactions

Contact Info

Product

Resources

About