Novel Inhibitory Function of the Rhizomucor miehei Lipase Propeptide and Three-Dimensional Structures of Its Complexes with the Enzyme

TY - JOUR

T1 - Novel Inhibitory Function of the Rhizomucor miehei Lipase Propeptide and Three-Dimensional Structures of Its Complexes with the Enzyme

AU - Moroz, Olga V.

AU - Blagova, Elena

AU - Reiser, Verena

AU - Saikia, Rakhi

AU - Dalal, Sohel

AU - Jørgensen, Christian Isak

AU - Bhatia, Vikram K.

AU - Baunsgaard, Lone

AU - Andersen, Birgitte

AU - Svendsen, Allan

AU - Wilson, Keith S.

N1 - © 2019 American Chemical Society

PY - 2019/6/7

Y1 - 2019/6/7

N2 - Many proteins are synthesized as precursors, with propeptides playing a variety of roles such as assisting in folding or preventing them from being active within the cell. While the precise role of the propeptide in fungal lipases is not completely understood, it was previously reported that mutations in the propeptide region of the Rhizomucor miehei lipase have an influence on the activity of the mature enzyme, stressing the importance of the amino acid composition of this region. We here report two structures of this enzyme in complex with its propeptide, which suggests that the latter plays a role in the correct maturation of the enzyme. Most importantly, we demonstrate that the propeptide shows inhibition of lipase activity in standard lipase assays and propose that an important role of the propeptide is to ensure that the enzyme is not active during its expression pathway in the original host.

AB - Many proteins are synthesized as precursors, with propeptides playing a variety of roles such as assisting in folding or preventing them from being active within the cell. While the precise role of the propeptide in fungal lipases is not completely understood, it was previously reported that mutations in the propeptide region of the Rhizomucor miehei lipase have an influence on the activity of the mature enzyme, stressing the importance of the amino acid composition of this region. We here report two structures of this enzyme in complex with its propeptide, which suggests that the latter plays a role in the correct maturation of the enzyme. Most importantly, we demonstrate that the propeptide shows inhibition of lipase activity in standard lipase assays and propose that an important role of the propeptide is to ensure that the enzyme is not active during its expression pathway in the original host.

UR - http://www.scopus.com/inward/record.url?scp=85067104272&partnerID=8YFLogxK

U2 - 10.1021/acsomega.9b00612

DO - 10.1021/acsomega.9b00612

M3 - Article

AN - SCOPUS:85067104272

SN - 2470-1343

VL - 4

SP - 9964

EP - 9975

JO - ACS Omega

JF - ACS Omega

IS - 6

ER -