@article {46914,
	title = {Structural studies on 10-hydroxygeraniol dehydrogenase: a novel linear substrate-specific dehydrogenase from Catharanthus roseus},
	journal = {Proteins-Structure Function and Bioinformatics},
	volume = {88},
	year = {2020},
	month = {SEP},
	pages = {1197-1206},
	type = {Article},
	abstract = {<p>Conversion of 10-hydroxygeraniol to 10-oxogeranial is a crucial step in iridoid biosynthesis. This reaction is catalyzed by a zinc-dependent alcohol dehydrogenase, 10-hydroxygeraniol dehydrogenase, belonging to the family of medium-chain dehydrogenase/reductase (MDR). Here, we report the crystal structures of a novel 10-hydroxygeraniol dehydrogenase from Catharanthus roseus in its apo and nicotinamide adenine dinucleotide phosphate (NADP(+)) bound forms. Structural analysis and docking studies reveal how subtle conformational differences of loops L1, L2, L3, and helix alpha 9{\textquoteright} at the orifice of the catalytic site confer differential activity of the enzyme toward various substrates, by modulating the binding pocket shape and volume. The present study, first of its kind, provides insights into the structural basis of substrate specificity of MDRs specific to linear substrates. Furthermore, comparison of apo and NADP(+) bound structures suggests that the enzyme adopts open and closed states to facilitate cofactor binding.</p>
},
	keywords = {10-hydroxygeraniol dehydrogenase, iridoid biosynthesis, medium-chain dehydrogenase, monoterpene indole alkaloids, reductase, X-ray crystallography},
	issn = {0887-3585},
	doi = {10.1002/prot.25891, Early Access Date = MAR 2020},
	author = {Sandholu, Anand S. and Mujawar, Sharmila P. and Ramakrishnan, Krithika and Thulasiram, Hirekodathakallu V. and Kulkarni, Kiran}
}
@article {47106,
	title = {Dynamic coupling analysis on plant sesquiterpene synthases provides leads for the identification of product specificity determinants},
	journal = {Biochemical and Biophysical Research Communications},
	volume = {536},
	year = {2021},
	month = {JAN },
	pages = {107-114},
	type = {Article},
	abstract = {<p>Sesquiterpene synthases catalyse cyclisation of farnesyl pyrophosphate to produce diverse sesquiterpenes. Despite utilising the same substrate and exhibiting significant sequence and structural homology, these enzymes form different products. Previous efforts were based on identifying the effect of divergent residues present at the catalytic binding pocket on the product specificity of these enzymes. However, the rationales deduced for the product specificity from these studies were not generic enough to be applicable to other phylogenetically distant members of this family. To address this problem, we have developed a novel approach combining sequence, structural and dynamical information of plant sesquiterpene synthases (SSQs) to predict product modulating residues (PMRs). We tested this approach on the SSQs with known PMRs and also on sesquisabinene synthase 1 (SaSQS1), a SSQ from Indian sandalwood. Our results show that the dynamical sectors of SSQs obtained from molecular dynamics simulation and their hydrophobicity and vicinity indices together provide leads for the identification of PMRs. The efficacy of the technique was tested on SaSQS1 using mutagenesis. To the best of our knowledge, this is a first technique of this kind which provides cues on PMRs of SSQs, with divergent phylogenetic relationship. (C) 2020 Elsevier Inc. All rights reserved.</p>
},
	keywords = {molecular dynamics, Product specificity, Sesquiterpene synthases, Statistical coupling analysis, X-ray crystallography},
	issn = {0006-291X},
	doi = {10.1016/j.bbrc.2020.12.041},
	author = {Singh, Sneha and Thulasiram, V, Hirekodathakallu and Sengupta, Durba and Kulkarni, Kiran}
}
