Figure 1.

Structures of Poly(β-L-Malic Acids) (PMLAs) and Their Degradation by PMLA Hydrolases In Vivo.

(A) Structures of α, β, and α,β types of polymalic acid. (B) PMLA hydrolases break down the first ester bond from OH-terminus while binding to the 12th malyl unit along the polymer chain towards the C-terminus [73]. (C) Intracellular trafficking of PMLA hydrolases and their extracellular activation. In typical eukaryotes, PMLA hydrolase binds to PMLA and remains inactive, carrying nuclear proteins into the nucleus while PMLA hydrolase remains at the surface of nuclear envelope. Cargo-discharged PMLA exits from the nucleus into the cytoplasm via nuclear pores; it binds to PMLA hydrolases that then translocate across the cell membrane where they are phosphorylated by membrane-bound tyrosine kinases, restoring their activity to degrade PMLAs extracellularly [74,75].