Proline, a unique amino acid that lacks a primary amino group, is a key building block of proteins and plays an important role in stress protection and redox balance of cells across multiple kingdoms. Pyrroline-5-carboxylate reductase (PYCR) is the final enzyme in proline biosynthesis, catalyzing the NAD(P)H-dependent reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline. Mutations in the PYCR1 gene alter mitochondrial function and cause the connective tissue disorder cutis laxa. Furthermore, PYCR1 is overexpressed in multiple cancers, and the PYCR1 knock-out suppresses tumorigenic growth, suggesting that PYCR1 is a potential cancer target. PYCR has been implicated in various cancers and has emerged as a potential therapeutic target. A study of mRNA profiles from 1,981 tumors identified PYCR1 as one of the most consistently overexpressed metabolic genes across 19 different cancer types. Additional studies highlight an abundance of PYCR1 in melanoma cells as compared with healthy melanocytes, indicating this enzyme as a potential therapeutic target in skin cancer treatment. Similarly, depletion of PYCR1 in different types of cancers, such as breast, prostate, and renal cell carcinoma, is associated with diminished cell proliferation and tumorigenic growth. Deficiencies in PYCR are also linked to inherited metabolic disorders. Certain mutations in the PYCR1 gene cause the autosomal recessive connective tissue disorder cutis laxa. The decrease in PYCR1 activity is thought to impair mitochondrial function, leading to developmental defects through increased apoptosis. Here you can see an AI-driven interpretation of a recent x-ray structure of human PYCR1 in its pentameric form (PDB code: 8TCX)

#molecularart ... #PYCR1 ... #xray ... #AI ... #cancer ... #proline ... #biosynthesis

Structure rendered with @proteinimaging, post-processed with @stylar.ai_official and depicted with @corelphotopaint