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Last update 08 May 2025

PLOD1

Last update 08 May 2025

Basic Info

Synonyms

LH1, LLH, Lysyl hydroxylase 1

+ [3]

Introduction

Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (By similarity). Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:10686424, PubMed:15854030, PubMed:8621606). These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links (Probable).

Drugs associated with PLOD1

Kyphoscoliotic EDS(UMass Chan Medical School)

Target

PLOD1

Mechanism

PLOD1 modulators

Active Org.

UMass Chan Medical School

Originator Org.

UMass Chan Medical School

Active Indication

Ehlers-Danlos Syndrome

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PLOD1

100 Translational Medicine associated with PLOD1

0 Patents (Medical) associated with PLOD1

641

Literatures (Medical) associated with PLOD1

01 Apr 2025·Biochimica et Biophysica Acta (BBA) - Bioenergetics

Structural integrity and near-infrared absorption of the LH1 complex of Thermochromatium tepidum: Influence from the C-terminal lysine residues of LH1 α-polypeptide

Article

Author: Yan, Yi-Hao ; Zhang, Jian-Ping ; Yu, Long-Jiang ; Zou, Mei-Juan ; Li, Yu-Qian

The light-harvesting complex 1-reaction center (LH1-RC) photosystem of the thermophilic purple sulfur bacterium Thermochromatium (Tch.) tepidum exhibits a near-infrared LH1-Q_y absorption band at 915 nm as regulated by binding calcium ions (Ca²⁺). To further explore the possible involvement of the C-terminal lysine residues of the LH1 α-polypeptide, we have genetically engineered a Rhodospirillum rubrum mutant strain to yield the site-directed modifications of the terminal α-Lys60 and α-Lys61 residues of Tch. tepidum LH1 α-polypeptide. Four of the LH1 mutants exhibit a subtle blue shift of 3 nm upon deletion or substitution of the lysine residues, however, they display over 40 nm blue shifts upon Ca²⁺ removal by ethylene diamine tetraacetic acid (EDTA) treatment. Spectral properties of native Tch. tepidum LH1-RC, the LH1-only, and the mutant LH1-only complexes are compared on a structural basis, which allows us to conclude that the C-terminal lysine residues and the Ca²⁺ binding synergistically affect the structural integrity and the LH1-Q_y spectral shift. This work demonstrates a methodology for the genetic manipulation of photosynthetic proteins lacking mutagenesis information, and may shed light on understanding the detailed structural factors involved in tuning the LH1-Q_y absorption.

01 Apr 2025·Archives of Biochemistry and Biophysics

A novel tRNA-Derived Fragment, tRF-20-M0NK5Y93 inhibits the malignant progression of non-small cell lung cancer by mediating PLOD1

Article

Author: Chen, Xiaojie ; Chen, Dong ; Chen, Qin ; Wu, Fengjie ; Wu, Lixin

OBJECTIVENon-small cell lung cancer (NSCLC) constitutes a common malignant tumor characterized by substantial mortality rates. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have been implicated in the progression of various cancers, including NSCLC. However, to date, only a limited number of tsRNAs have been reported to be involved in the development of NSCLC. Hence, the present study aimed to investigate the potential roles of tsRNAs in the progression of NSCLC.MATERIALS AND METHODSA total of forty-six patients with NSCLC who underwent surgical resection were enrolled in this study. The expression patterns of tRNA-derived fragments (tRFs) in tumor and normal tissues of 6 NSCLC cases were investigated using RNA-sequencing assay. Cell viability, proliferation capacity, and migratory ability were measured utilizing the CCK-8, colony formation, and Transwell assays, respectively. Furthermore, cell apoptosis was evaluated by applying flow cytometry. The xenograft tumor model was constructed to observe tumor growth. The relationship between tRF-20-M0NK5Y93 and PLOD1 was clarified using the luciferase and RIP assays.RESULTSThe RNA-sequencing assay revealed a significant decrease in the expression of tRF-20-M0NK5Y93 in tumor tissues. In line with this finding, qRT-PCR analysis further confirmed a meaningful downregulation of tRF-20-M0NK5Y93 in 46 patient samples with NSCLC. Importantly, this downregulated expression was strongly correlated with reduced patient survival. Additionally, overexpression of tRF-20-M0NK5Y93 was found to inhibit the proliferation and migration capabilities of NSCLC cells, leading to suppressed tumor growth and accelerated apoptosis. Furthermore, tRF-20-M0NK5Y93 was capable of binding to PLOD1, thereby negatively regulating its expression. Notably, the restoration of PLOD1 expression was able to counteract the inhibitory effects of enforced tRF-20-M0NK5Y93 on NSCLC cell proliferation, migration, and apoptosis.CONCLUSIONThe expression level of tRF-20-M0NK5Y93 was found to be decreased in NSCLC. Overexpressed tRF-20-M0NK5Y93 exhibited inhibitory effects on NSCLC cell proliferation and migration, accelerated apoptosis, and suppressed tumor growth by targeting PLOD1. These findings highlight tRF-20-M0NK5Y93 as a promising target for NSCLC therapy.

01 Apr 2025·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Increasing collagen synthesis in fibroblasts: The roles of PCL microspheres and the SAMD11–PLOD1 axis in skin rejuvenation

Article

Author: Cao, Mibu ; Zhang, Youliang ; Ge, Yuanlong ; Tao, Li ; Luo, Shengkang ; Zou, Ying ; Zhou, Lingcong ; Wu, Shu ; Zhou, Haoxian

The degradation of extracellular matrix proteins such as collagen and elastin with aging leads to skin sagging. Polycaprolactone (PCL) microspheres are used as facial fillers because of their ability to provide volume, biodegradability, and collagen-stimulating properties. The direct biological effects of PCL microspheres on fibroblasts, particularly in stimulating sustained collagen production, require further investigation. We detected the safety and effect of PCL microspheres on human fibroblasts and investigated new collagen synthesis and the thickness of C57BL/6 mouse skin. Through an RNA-seq analysis of differentially expressed genes, we identified a key regulator of collagen production in PCL-stimulated fibroblasts. Our research revealed that PCL microspheres are safe for human fibroblasts, promoting their proliferation and increasing new collagen synthesis and skin thickness. We identified sterile alpha motif domain containing 11 (SAMD11) as a key regulator of collagen production in PCLstimulated fibroblasts through an RNA-seq analysis. By increasing SAMD11 expression, PCL microspheres increase collagen synthesis and rejuvenate skin through the upregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1). This study elucidates the mechanism by which SAMD11 regulates the effects of PCL microspheres as collagen stimulants for skin rejuvenation, providing a foundation for the future development and refinement of similar materials.

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PLOD1

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