Biology subjects

Venugopal, H.

Publications and source records attributed to Venugopal, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Structural basis for inefficient G protein coupling by Frizzled receptors

Frizzleds (FZDs) are class F G protein-coupled receptors (GPCRs) that primarily signal through Dishevelled (DVL) to initiate Wnt signalling, with evidence for context-specific coupling to heterotrimeric G proteins. Every FZD-G protein structure to date has been determined without an agonist, implying that agonist binding is not required for stable complex formation in vitro and directly contradicting the difficulty of demonstrating G protein coupling in cells. All these structures contain unassigned density between the receptor and the heterotrimeric G protein. From structures generated by single-particle cryo-electron microscopy (cryo-EM) of FZD7-Gs and FZD5-Gq, we identify this density as the detergent lauryl maltose neopentyl glycol (LMNG), which bridges the receptor and G protein to stabilise a weak, shallow interface. Absence of LMNG - in biochemical preparations and molecular dynamics simulations - destabilises the complex, showing that constitutive FZD-G protein engagement is intrinsically weak. The weak G protein coupling is governed by a conserved intracellular interface that when mutated differentially influences DVL and G protein signalling. Our findings show that LMNG has masked the instability of purified FZD-G protein complexes and provide the structural basis of FZDs as inherently weak G protein activators that are predisposed to DVL signalling.

biochemistry↗

bioRxiv2026

Conserved T cell receptor usage underpins recognition of CD1c presenting a mycobacterial lipid

The mechanism by which T cell receptors (TCR) recognise mycobacterial lipids presented by CD1 family members not well understood. We used CD1c tetramers loaded with the mycobacterial phosphomycoketide (PM) or mannosyl-PM (MPM) to isolate T cells ex vivo in healthy blood donors and in individuals from a tuberculosis (TB)-endemic region of South Africa, with higher frequencies observed in individuals from the TB-endemic region. High throughput analysis of >200 paired CD1c-mycoketide tetramer+ {beta}TCRs identified a conserved TCR motif, encoded by TRBV4-1 or TRBV7-9 variable region genes in greater than half of TCRs sequenced. A cryo-EM structure of a TRBV7-9+ TCR in complex with CD1c-PM demonstrated that the TCR bound to the F side of CD1c, directly contacting the phospholipid antigen and F-portal residues. Analysis of multiple T cell clones interacting with CD1c mutants suggested that this TCR docking mode is representative of the larger TRBV7-9+ T cell population. Collectively, this study provides insight into mycobacterial lipid-antigen recognition by CD1c-restricted T cells. SummaryCao and Soliman et al study CD1c-restricted human T cells that recognize mycobacterial phosphomycoketide lipids, where they are shown to be more frequent in blood a TB-endemic region. The authors describe a strong TCR-{beta} repertoire bias and use cryoEM to provide a high-resolution structure of an archetypal TCR engaging CD1c in complex with a mycobacterial lipid.

immunology↗

bioRxiv2026

Cryo-EM structure of human LRRC15 reveals the basis of therapeutic antibody recognition

Leucine-rich repeat containing 15 (LRRC15) is a structural uncharacterised membrane protein, which is highly upregulated in cancer-associated fibroblasts and enriched in desmoplastic tumours including pancreatic, breast and head-and-neck cancers, where it is associated with therapy resistance. The LRRC15-targeting antibody-drug conjugate samrotamab vedotin has advanced into Phase I clinical evaluation, yet mechanistic understanding of how samrotamab engages its target has remained elusive in the absence of structural data. Here, using hydrogen-deuterium exchange mass spectrometry and cryo-electron microscopy, we define the samrotamab epitope on LRRC15 and determine the structure of the LRRC15-samrotamab complex to 2.6 [A] resolution - the first high-resolution structure of this receptor. Samrotamab engages a membrane-proximal epitope within the C-terminal leucine-rich repeat region, leaving the canonical concave surface fully exposed for potential interactions. The lateral binding mode of samrotamab and the open arc geometry of LRRC15 provide a structural rationale for why antibody occupancy may leave signalling-competent surfaces intact. Guided by these insights, we computationally designed minibinders targeting the concave surface, identifying multiple binders with nanomolar affinity. Together, our work establishes the first structural framework for LRRC15, defines the molecular basis of therapeutic antibody recognition, and identifies the concave surface as a promising target for next-generation LRRC15-directed therapeutics.

biochemistry↗

bioRxiv2026

PartiNet is a dynamic adaptive neural network for high-performance particle picking in cryo-electron microscopy

Accurate, efficient and autonomous particle picking is a major bottleneck in high-resolution cryo-electron microscopy (cryo-EM). We introduce PartiNet, an Artificial Intelligence (AI)-based particle picker with size-agnostic detection and pre-trained models that eliminate manual parameter specification and dataset-specific training, pioneering dynamic neural network inference for single particle cryo-EM pipeline. Unlike static architectures, PartiNet employs a dynamic framework that adjusts network complexity in real-time based on perceived micrograph quality. This adaptive approach accelerates inference up to 7-fold compared to existing tools without sacrificing particle selection quality. Training on diverse protein datasets showed that PartiNet improves particle yields, enhances sampling of rare orientations, and is compatible with on-the-fly workflows. Comprehensive evaluation on benchmark datasets and validation on a new dataset of the chromatin remodeler MORC2 demonstrates superior precision and recall, with the ability to detect heterogeneous protein species, leading to more complete structural models and consistently higher-resolution reconstructions.

molecular biology↗

bioRxiv2025

Structures of tRNA-bound CRISPR-Cas13 reveal universal HEPN RNase mechanisms

Ribonucleases (RNases) are ubiquitous drivers of RNA metabolism across life. Higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing RNases form a nuclease superfamily whose mechanisms of substrate selection and catalysis remain poorly understood. Here, we report substrate preferences for diverse Cas13 HEPN RNases, revealing precise cleavage of tRNA anticodons and acceptor stems. Using cryo-EM, we present a series of activated Leptotrichia buccalis Cas13a (LbuCas13a) structures engaged with substrate tRNA. We show LbuCas13a captures tRNA through shape- and sequence-specific recognition, cleaving U-rich anticodons independently of tRNA modifications. Leveraging these insights, we reprogram Cas13 specificity and engineer variants with accelerated RNase activity. These findings establish the molecular basis for Cas13 tRNase activity and indicate that the HEPN RNase superfamily obeys universally conserved mechanisms of substrate recognition and catalysis.

biochemistry↗

bioRxiv2025

Structure-guided allosteric modulation of the delta opioid receptor

Opioid analgesics remain essential for pain management but are associated with significant adverse effects, including respiratory depression, tolerance, and dependence. The {delta}-opioid receptor ({delta}OR) represents a promising therapeutic target for developing safer opioid analgesics with reduced adverse effects compared to conventional -opioid receptor-targeting drugs. Positive allosteric modulators (PAMs) offer advantages over direct agonists by enhancing endogenous opioid signaling while preserving natural spatiotemporal activation patterns, potentially avoiding tolerance and dependence issues. Here, we present high-resolution cryo-EM structures of {delta}OR complexed with the peptide agonist DADLE and the PAM MIPS3614, revealing a novel lipid-facing allosteric binding site formed by transmembrane helices 2, 3, and 4. MIPS3614 stabilizes the active receptor conformation through a critical hydrogen bond with residue N1313.35 in the conserved sodium binding site, a key regulatory region controlling GPCR activation. Comprehensive mutagenesis, molecular dynamics simulations, and structure-activity relationships validate this proposed mechanism. Structure-guided optimization yielded MIPS3983 with enhanced binding affinity and retained cooperativity. Our findings establish the first molecular framework for {delta}OR allosteric modulation and provide a structural foundation for the rational design of safer opioid therapeutics.

pharmacology and toxicology↗

bioRxiv2025

A Protein Antibiotic Inhibits the BAM Complex to Kill Without Cell Entry

Many antibiotics are ineffective against Gram-negative pathogens such as Pseudomonas aeruginosa because they cannot penetrate the bacterial outer membrane. Here, we show that protein antibiotics called L-type pyocins kill P. aeruginosa by inhibiting the {beta}-barrel assembly machinery (BAM) complex at the cell surface, halting outer-membrane protein assembly. Using single-particle cryo-electron microscopy, we show that L-type pyocins bind a surface-exposed region of BamA and deploy a C-terminal peptide that competitively inhibits the BAM complex, demonstrating that cell entry is not required for antibiotic activity. We combine genetics, multi-omics and cryo-electron tomography to show that BAM complex inhibition by L-type pyocins or the peptide antibiotic darobactin triggers a multifaceted transcriptomic, proteomic and morphological response. Despite this, BAM inhibition ultimately leads to a catastrophic loss of membrane integrity and cell death. These results validate BAM as a target for antibiotics that do not enter the cell and define an engineerable system for their development.

microbiology↗

bioRxiv2025

Structural basis for Porcupine inhibition

Wnt signalling is essential for embryonic development and tissue homeostasis, and its dysregulation is associated with multiple types of cancer. Porcupine (PORCN), an endoplasmic reticulum (ER)-resident membrane-bound O-acyltransferase, catalyses the palmitoylation of all 19 human Wnts--a critical modification required for their secretion and activity. This central role makes PORCN an attractive therapeutic target for Wnt-driven cancers, with several inhibitors currently in clinical trials. Here, we present high-resolution cryo-electron microscopy structures of human PORCN in complex with the inhibitors C59 (2.4 [A]) and ETC159 (2.6 [A]), as well as in a ligand-free state (3.3 [A]). These structures reveal critical ordered water molecules that form a hydrogen-bonding network within the active site, mediating inhibitor binding. Our docking simulations of diverse PORCN inhibitors demonstrate that despite their different chemical scaffolds, these compounds adopt similar conformations within the acyl-CoA binding site and are also engaged through a conserved water molecule. Our findings provide a structural foundation for the rational design of next-generation PORCN inhibitors with improved pharmacological properties for cancer therapy.

biochemistry↗

bioRxiv2025

Cryo-EM reveals a new allosteric binding site at the M5 mAChR

The M5 muscarinic acetylcholine receptor (M5 mAChR) represents a promising therapeutic target for neurological disorders. However, the high conservation of its orthosteric binding site has posed significant challenges for drug development. While selective positive allosteric modulators (PAMs) offer a potential solution, a structural understanding of the M5 mAChR and its allosteric binding sites has remained limited. Here, we present a 2.8 [A] cryo-electron microscopy structure of the M5 mAChR complexed with heterotrimeric Gq protein and the agonist iperoxo, completing the active-state structural characterization of the mAChR family. To identify the binding site of M5-selective PAMs, we implemented an integrated approach combining mutagenesis, pharmacological assays, structural biology, and molecular dynamics simulations. Our mutagenesis studies revealed that selective M5 PAMs bind outside previously characterized M5 mAChR allosteric sites. Subsequently, we obtained a 2.1 [A] structure of M5 mAChR co-bound with acetylcholine and the selective PAM VU6007678, revealing a novel allosteric pocket at the extrahelical interface between transmembrane domains 3 and 4 that was confirmed through mutagenesis and simulations. These findings demonstrate the diverse mechanisms of allosteric regulation in mAChRs and highlight the value of integrating pharmacological and structural approaches to identify novel allosteric binding sites.

pharmacology and toxicology↗

bioRxiv2025

Molecular basis of ligand binding and receptor activation at the human A3 adenosine receptor

Adenosine receptors (ARs: A1AR, A2AAR, A2BAR, and A3AR) are crucial therapeutic targets, yet developing selective, efficacious drugs remains challenging. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of the human A3AR in three distinct functional states: bound to the endogenous agonist adenosine, the clinically relevant agonist Piclidenoson, and the covalent antagonist LUF7602. These structures, complemented by mutagenesis and pharmacological studies, reveal a unique A3AR activation mechanism involving an extensive hydrogen bond network from the extracellular surface down to the orthosteric binding site. In addition, we identify a cryptic pocket that accommodates the N6-iodobenzyl group of Piclidenoson through a ligand-dependent conformational change of M1745.35. Our comprehensive structural and functional characterization of A3AR advances understanding of adenosine receptor pharmacology and establishes a foundation for developing more selective therapeutics for various disorders including inflammatory diseases, cancer, and glaucoma. TeaserStructures of the A3AR in different conformations reveal a unique activation mechanism and cryptic binding pocket.

pharmacology and toxicology↗

bioRxiv2024

Inhibiting heme-piracy by pathogenic Escherichia coli using de novo-designed proteins

Iron is an essential nutrient for most bacteria and is often growth-limiting during infection, due to the host sequestering free iron as part of the innate immune response. To obtain the iron required for growth, many bacterial pathogens encode transporters capable of extracting the iron-containing cofactor heme directly from host proteins. Pathogenic E. coli and Shigella spp. produce the outer membrane transporter ChuA, which binds host hemoglobin and extracts its heme cofactor, before importing heme into the cell. Heme extraction by ChuA is a dynamic process, with the transporter capable of rapidly extracting heme from hemoglobin in the absence of an external energy source, without forming a stable ChuA-hemoglobin complex. In this work, we utilise a combination of structural modelling, Cryo-EM, X-ray crystallography, mutagenesis, and phenotypic analysis to understand the mechanistic detail of this process. Based on this understanding we utilise artificial intelligence-based protein design to create binders capable of inhibiting E. coli growth by blocking hemoglobin binding to ChuA. By screening a limited number of these designs, we identify several binders that inhibit E. coli growth at low nanomolar concentrations, without experimental optimisation. We determine the structure of a subset of these binders, alone and in complex with ChuA, demonstrating that they closely match the computational design. This work demonstrates the utility of de novo-designed proteins for inhibiting bacterial nutrient uptake and uses a workflow that could be applied to integral membrane proteins in other organisms.

biochemistry↗

bioRxiv2024

MORC2 phosphorylation fine tunes its DNA compaction activity

Variants in the poorly characterised oncoprotein, MORC2, a chromatin remodelling ATPase, lead to defects in epigenetic regulation and DNA damage response. The C-terminal domain (CTD) of MORC2, frequently phosphorylated in DNA damage, promotes cancer progression, but its role in chromatin remodelling remains unclear. Here, we report a molecular characterisation of full-length, phosphorylated MORC2, demonstrating its preference for binding open chromatin and functioning as a DNA sliding clamp. We identified a phosphate interacting motif within the CTD that dictates ATP hydrolysis rate and cooperative DNA binding. The DNA binding impacts several structural domains within the ATPase region. We provide the first visual proof that MORC2 induces chromatin remodelling through ATP hydrolysis-dependent DNA compaction, regulated by its phosphorylation state. These findings highlight phosphorylation of MORC2 CTD as a key modulator of chromatin remodelling, presenting it as a potential therapeutic target.

molecular biology↗

bioRxiv2024

High-affinity PQQ import is widespread in Gram-negative bacteria

PQQ is a soluble redox cofactor used by diverse bacteria to oxidise fuel compounds as a source of electrons for the respiratory chain. Many Gram-negative bacteria that encode PQQ-dependent enzymes do not possess the biosynthetic machinery for its production and instead obtain it from the environment. To achieve this the bacterium Escherichia coli uses the TonB-dependent transporter PqqU as a high-affinity PQQ importer, allowing it to use PQQ at an external concentration as low as 1 nM. Here, we show that PqqU achieves this by binding PQQ with a very high affinity. Using cryo-electron microscopy we determine the structure of the PqqU-PQQ complex at a resolution of 1.99 [A], revealing that the extracellular loops of PqqU undergo significant conformational changes upon PQQ binding, which captures the cofactor in an internal cavity. This cavity likely facilitates an airlock-style gating mechanism that prevents non-specific import through PqqU. Using structural modelling we show that the change in PqqU structure upon PQQ binding precludes the binding of bacteriophage, which targets it as a cell surface receptor. Guided by the PqqU-PQQ complex structure we use phenotypic analysis to identify the amino acids essential for PQQ import and leverage this information to map the presence of PqqU across Gram-negative bacteria. This reveals that PqqU is encoded by Gram-negative bacteria from at least 22 phyla from diverse habitats, including those found in aquatic, soil, host-associated, and extreme environments. This indicates that PQQ is a ubiquitous nutrient in many environments, and an important cofactor for bacteria that adopt diverse lifestyles and metabolic strategies. Significance StatementMany enzymes form complexes with molecules called cofactors to perform their function. PQQ is a cofactor used by bacterial enzymes that provide energy by breaking down food molecules. While some bacteria make their own PQQ, other bacteria use the transport protein PqqU to bind PQQ from the environment and import it into their cells. We show that PqqU binds PQQ very tightly, allowing bacteria to acquire it at very low concentrations. Using cryo-electron microscopy we image the PqqU-PQQ complex on an atomic level, revealing how PQQ is bound so tightly. Using this the information to analyse microbial genomes, we show that PQQ scavenging is employed by diverse bacteria, implying that PQQ is an important common good of diverse microbiomes.

biochemistry↗

bioRxiv2024

Obtaining high-resolution cryo-EM structures using a common LaB6, 120-keV electron microscope equipped with a sub 200-keV optimised direct electron detector.

Cryo-electron microscopy (Cryo-EM) single particle analysis (SPA) has become a major structural biology technique in recent years. High-resolution cryo-EM typically requires higher voltage cryo-TEMs with coherent FEG sources, stable columns, autoloader systems and direct electron detectors. These setups are specialised for Cryo-EM work and are expensive to establish and maintain. More recently the concept of using 100-keV cryo-TEMs has been introduced as a way to make cryo-EM more affordable and hence accessible to a larger group of researchers. So far, the implementation of these 100-keV cryo-TEMs have relied on specialised microscopes with FEG sources as well as more stable optics than usually present on the common 120-keV TEMs. We here explored whether a standard 120-keV TEM, commonly available at many laboratories worldwide, can be upgraded with a direct electron detector and its suitability for high-resolution cryo-EM using a standard side entry cryo-holder. Using this imaging configuration, we were successful in achieving a 2.65[A] reconstruction for standard apoferritin. We were also able to resolve a more challenging small 64kDa protein haemoglobin to 4.33[A]. Furthermore, we were able to solve an asymmetric 153 kDa membrane protein GPCR (M4 muscarinic acid receptor) to a resolution of 4.4[A]. Importantly, all these results were achieved using a standard automated data collection routine implemented through SerialEM, making it feasible to collect large cryo-EM data sets with a side entry cryo-holder. These results showcase a potentially widely accessible solution to obtaining interpretable cryo-EM structures. Furthermore, we envisage that this imaging configuration gives an option for many EM facilities and laboratories to set up a high-quality cryo-EM SPA sample screening capability without the need to procure costly specialised Cryo-TEMs. This could help to considerably lower the economic entry barrier for cryo-EM SPA and contribute to the "democratisation" of cryo-EM.

biophysics↗

bioRxiv2024

Structural insights into the human P2X1 receptor and ligand interactions

The P2X1 receptor is a trimeric ligand-gated ion channel that plays a pivotal role in urogenital and immune functions. Consequently, it offers numerous potential indications for novel drug treatments. Unfortunately, the progress of drug discovery targeting the P2X1 receptor has been impeded by the absence of structural information. To gain deeper insights into the binding site of the P2X1 receptor, we employed cryogenic electron microscopy (cryo-EM) to elucidate the structures of the P2X1 receptor in both an ATP-bound desensitised state and an NF449-bound closed state. NF449 is a potent P2X1 receptor antagonist and engages with the receptor in a distinctive manner. To gain insights into the molecular machinery governing receptor inhibition and activation and better understand P2X1 receptor ligand subtype selectivity, critical P2X1 receptor residues involved in ligand binding were mutated. Radioligand binding assays with [3H]-,{beta}-methylene ATP and intracellular calcium influx were employed to assess the effect of these mutations on ligand binding and receptor activation, thereby validating key ligand-receptor interactions. This research expands our understanding of the P2X1 receptor structure at a molecular level and opens new avenues for in silico drug design targeting the P2X1 receptor.

pharmacology and toxicology↗

bioRxiv2024

Quinone extraction drives atmospheric carbon monoxide oxidation in bacteria

Diverse bacteria and archaea use atmospheric carbon monoxide (CO) as an energy source during long-term survival. This process enhances the biodiversity of soil and marine ecosystems globally and removes 250 million tonnes of a toxic, climate-relevant pollutant from the atmosphere each year. Bacteria use [MoCu]-carbon monoxide dehydrogenases (Mo-CODH) to convert CO to carbon dioxide, then transfer the liberated high-energy electrons to the aerobic respiratory chain. However, given no high-affinity Mo-CODH has been purified, it is unknown how these enzymes oxidise CO at low concentrations and interact with the respiratory chain. Here we resolve these knowledge gaps by analysing Mo-CODH (CoxSML) and its hypothetical partner CoxG from Mycobacterium smegmatis. Kinetic and electrochemical analyses show purified Mo-CODH is a highly active high-affinity enzyme (Km = 139 nM, kcat = 54.2 s-1). Based on its 1.85 [A] resolution cryoEM structure, Mo-CODH forms a CoxSML homodimer similar to characterised low-affinity homologs, but has distinct active site coordination and narrower gas channels that may modulate affinity. We provide structural, biochemical, and genetic evidence that Mo-CODH transfers CO-derived electrons to the aerobic respiratory chain via the membrane-bound menaquinone-binding protein CoxG. Consistently, CoxG is required for CO-driven respiration, extracts menaquinone from mycobacterial membranes, and binds quinones in a hydrophobic pocket. Finally, we show that Mo-CODH and CoxG genetically and structurally associate in diverse bacteria and archaea. These findings reveal the basis of a biogeochemically and ecologically important process, while demonstrating that the newly discovered process of long-range quinone transport is a general mechanism of energy conservation, which convergently evolved on multiple occasions.

biochemistry↗

bioRxiv2023

Structure of a Rhs effector clade domain identifies new mechanistic insights into type VI secretion system toxin delivery.

The type VI secretion system (T6SS) is a molecular machine utilised by many Gram-negative bacteria to deliver antibacterial toxins directly into adjacent bacteria, often providing a competitive advantage. Rearrangement hotspot (Rhs) effectors are known T6SS cargo effectors, but the precise delivery and activation of these toxins is poorly defined. We present the structure of a novel T6SS Rhs effector (Tse15) from the multidrug resistant nosocomial pathogen Acinetobacter baumannii. Tse15 forms a triple layered y-cocoon Rhs domain with an N-terminal -helical clade domain and an unfolded C-terminal toxin domain located entirely inside the Rhs cage. We identify that Tse15 is cleaved into three domains, through two independent auto-cleavage events involving aspartyl protease activity for toxin self-cleavage and a nucleophilic glutamic acid for the cleavage of the N-terminal clade domain. Proteomic analyses showed that the N-terminal clade and toxin domains, but not the y-strand rich Rhs cage, are delivered outside of the cell, suggesting a novel mechanism for Rhs toxin delivery and activation. Our findings suggest that this delivery mechanism requires an interaction between the N-terminal clade and toxin domains, with the clade domain acting as the internal chaperone to mediate tethering of the toxin to the T6SS machinery. Conservation of the clade domain in other Gram-negative bacteria suggest this may be a common mechanism for T6SS toxin delivery.

microbiology↗

bioRxiv2023

Cryo-EM structures of human arachidonate 12S-Lipoxygenase (12-LOX) bound to endogenous and exogenous inhibitors

Human 12-lipoxygenase (12-LOX) is an enzyme involved in platelet activation and is a promising target for antiplatelet therapies. Despite the clinical importance of 12-LOX, the exact mechanisms of how it affects platelet activation are unclear, and the lack of structural information has limited drug discovery efforts. In this study, we used single-particle cryoelectron microscopy to determine the high-resolution structures (1.7 [A] - 2.8 [A]) of human 12-LOX for the first time. Our results showed that 12-LOX can exist in multiple oligomeric states, from monomer to hexamer, which may impact its catalytic activity and membrane association. We also identified different conformations within a 12-LOX dimer, likely representing different time points in its catalytic cycle. Furthermore, we were able to identify small molecules bound to the 12-LOX structures. The active site of the 12-LOX tetramer is occupied by an endogenous 12-LOX inhibitor, a long-chain acyl-Coenzyme A. Additionally, we found that the 12-LOX hexamer can simultaneously bind to arachidonic acid and ML355, a selective 12-LOX inhibitor that has passed a phase I clinical trial for treating heparin-induced thrombocytopenia and has received fast-track designation by the FDA. Overall, our findings provide novel insights into the assembly of 12-LOX oligomers, its catalytic mechanism, and small molecule binding, paving the way for further drug development targeting the 12-LOX enzyme. Key PointsO_LIThe first full-length structures of human arachidonate 12S-Lipoxygenase (12-LOX) C_LIO_LIReveals mechanisms of oligomeric and conformational states C_LIO_LIUncovers natural inhibitor of 12S-Lipoxygenase (12-lox) C_LIO_LIReveals a binding site of inhibitor ML355 C_LI

biochemistry↗