The Lid Domain in Lipases: Structural and Functional Determinant of Enzymatic Properties

Abstract

Lipases are important industrial enzymes. Most of the lipases operate at lipid–water interfaces enabled by a mobile lid domain located over the active site. Lid protects the active site and hence responsible for catalytic activity. In pure aqueous media, the lid is predominantly closed, whereas in the presence of a hydrophobic layer, it is partially opened. Hence, the lid controls the enzyme activity. In the present review, we have classified lipases into different groups based on the structure of lid domains. It has been observed that thermostable lipases contain larger lid domains with two or more helices, whereas mesophilic lipases tend to have smaller lids in the form of a loop or a helix. Recent developments in lipase engineering addressing the lid regions are critically reviewed here. After on, the dramatic changes in substrate selectivity, activity, and thermostability have been reported. Furthermore, improved computational models can now rationalize these observations by relating it to the mobility of the lid domain. In this contribution, we summarized and critically evaluated the most recent developments in experimental and computational research on lipase lids.

A stereospecific carboxyl esterase from Bacillus coagulans hosting nonlipase activity within a lipase‐like fold

“…C). hMGL, like all mono‐ and diacylglycerol lipases studied to date, belongs to the single α‐helix/loop lid lipase class . If BCE were in fact a true lipase, it would pertain to the large‐lid class characteristic of thermophilic lipases; however, in light of our activity data, it is likely that BCE belongs to an entirely different carboxyl esterase class altogether.…”

“…As mentioned above, the absence of interfacial activation for catalysis is contradictory to the presence of the lipase‐specific lid domain that would mediate this process. The BCE lid domain (residues 145–235) is particularly large, also with respect to the lids of the 21 other lipase members (of known structure) belonging to the large‐lid lipase subclass . Open and closed lid conformations have been crystallized for several lipases, however, the BCE lid was found in the closed conformation in all datasets collected to date, despite the absence or presence of glycerol bound at the active site (Fig.…”

X-Shaped ZIF-8 for Immobilization Rhizomucor miehei Lipase via Encapsulation and Its Application toward Biodiesel Production

“…The secondary structure related to RML can be altered by the conformation of lipase@ZIF-8. The lid opens to the substrate for a long period, which causes an increase in lipase activity due to the ease of access [35].…”

Semi‐rational evolution of the 3‐(3‐hydroxyalkanoyloxy)alkanoate (HAA) synthase RhlA to improve rhamnolipid production in Pseudomonas aeruginosa and Burkholderia glumae

“…These extra helices in RhlA Pa could therefore act as a similarly shaped cap‐domain previously reported in other α/β hydrolases (Fig. A) . Therefore, we hypothesized that residues 132‐190 in RhlA Pa could act as a key domain allowing substrate recognition and discrimination, whereby this α‐helix motif would be critical to substrate selectivity in RhlA Pa .…”