Effect of Cysteine Residue Substitution in the GCSAG Motif of the PMGL2 Esterase Active Site on the Enzyme Properties

Sequence and Structural Motifs Controlling the Broad Substrate Specificity of the Mycobacterial Hormone-Sensitive Lipase LipN

“… 13 , 15 Family IV members are further subdivided based on residues surrounding the conserved catalytic motifs, where distinct motifs impart unique catalytic activity and substrate selectivity to individual bHSLs. 23 − 25 For example, the presence of a tryptophan residue following the HGGG motif (HGGGW) is correlated with a strong preference for shorter ester substrates and the ability to catalyze difficult hydrolysis reactions with tertiary ester substrates. 23 , 26 − 28 Substrate preferences of bHSLs are also controlled by a variable N-terminal lid or cap domain whose features control substrate access, protein stability, and even promiscuous acyltransferase activity.…”

“…Common features across bHSLs are a core α/β hydrolase domain with conserved GxSxG and HGGG motifs containing the catalytic serine and oxyanion hole, respectively. The majority of bHSLs, including LipN, are classified into family IV of 15 bacterial esterase families. , Family IV members are further subdivided based on residues surrounding the conserved catalytic motifs, where distinct motifs impart unique catalytic activity and substrate selectivity to individual bHSLs. − For example, the presence of a tryptophan residue following the HGGG motif (HGGGW) is correlated with a strong preference for shorter ester substrates and the ability to catalyze difficult hydrolysis reactions with tertiary ester substrates. ,− Substrate preferences of bHSLs are also controlled by a variable N-terminal lid or cap domain whose features control substrate access, protein stability, and even promiscuous acyltransferase activity. − Unlike classic lipases, this N-terminal cap domain in bHSLs does not undergo significant structural changes or introduce latency into the kinetic mechanism of bHSLs. , …”