PGLS Human
Description
Biochemical Characteristics of PGLS Human Recombinant
PGLS Human Recombinant is produced in Escherichia coli as a 29.7 kDa protein fused to a 20-amino-acid N-terminal His-tag. Key properties include:
Its enzymatic activity supports NADPH production, which is vital for redox balance and biosynthesis in cancer cells .
Clinical Significance in Gastric Cancer
PGLS is overexpressed in gastric cancer tissues and correlates with poor prognosis. Key findings from proteomic and immunohistochemical studies include:
Table 1: PGLS Expression and Clinicopathological Correlations in Gastric Cancer35
| Clinicopathological Variable | PGLS-Positive (%) | Association |
|---|---|---|
| TNM Stage I vs. II–IV | 10/19 vs. 41/51 | Higher PGLS in advanced stages (p = 0.02) |
| Lymph Node Metastasis | 32/42 vs. 19/28 | No significant correlation |
| HER2-Negative Subtype | 72.9% sensitivity | Shorter OS (HR = 1.32, p = 0.016) |
| Male Patients | 34/45 vs. 17/25 | Worse OS (HR = 1.48, p = 2.1e-05) |
Pharmacological and Diagnostic Relevance
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Metabolic Targeting: PGLS inhibition disrupts NADPH synthesis, making it a potential therapeutic target for cancers reliant on the PPP .
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Bioconjugate Vaccines: Engineered PGLS variants enable glycosylation of carrier proteins (e.g., EPA–ComP fusion proteins), aiding vaccine development against pathogens like Klebsiella pneumoniae and Streptococcus pneumoniae .
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Anti-Inflammatory Applications: Methylated glycolipid derivatives of PGLS analogs (e.g., compound 34) show potent cytokine inhibition (67% TNF-α reduction at 10 µg/mL) .
Research Applications
Product Specs
Q&A
Basic Research Questions
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What is PGLS and why is it essential for human evolutionary studies?
Phylogenetic Generalized Least Squares (PGLS) is a statistical method that accounts for phylogenetic relationships when analyzing trait correlations across species. It is crucial for human evolutionary studies because traditional non-phylogenetic methods can yield misleading results by failing to incorporate trait co-variation among species resulting from shared evolutionary history.
Unlike conventional regression analyses, PGLS considers the phylogenetic position of each species when predicting phenotypic traits, producing more accurate assessments of whether humans are statistical "outliers" for traits like brain size. This makes PGLS invaluable when investigating human uniqueness quantitatively against our evolutionary relatives .
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How does PGLS methodology differ from standard regression approaches?
Standard regression approaches (like ordinary least squares) assume independence of data points, which is violated when analyzing cross-species data because closely related species share traits due to common ancestry. This violation can lead to significantly misleading results—for example, one study using non-phylogenetic methods suggested the human brain is only 10% larger than expected for a primate of human body mass .
PGLS addresses this fundamental issue by:
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Incorporating evolutionary relationships through a phylogenetic tree
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Accounting for expected trait similarities based on relatedness
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Modeling the evolutionary process (through Brownian motion or Ornstein-Uhlenbeck models)
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Properly evaluating individual species' deviations from expected patterns
This methodological difference is critical when evaluating uniqueness claims about human traits .
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What data prerequisites are necessary for conducting a valid PGLS analysis of human traits?
A valid PGLS analysis investigating human traits requires:
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Phylogenetic tree: A well-supported evolutionary tree including humans, extinct hominins (when relevant), and comparative species (typically primates)
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Trait measurements: Accurate phenotypic data (e.g., brain measurements, body mass) for all included species
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Sex-specific data: When possible, sex-specific measurements should be used; for example, female body mass values are often preferred as they typically have stronger linkage to ecological and life-history factors
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Sample representation: Sufficient taxonomic sampling to provide context for human values
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Control variables: Additional variables that might influence the trait of interest (e.g., controlling for body mass when analyzing brain size)
Without these data components, PGLS analysis cannot produce valid statistical inferences about human evolutionary patterns.
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Research Application Examples
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How has PGLS been applied to quantify human brain size evolution?
PGLS has been instrumental in quantifying human brain size evolution through several key applications:
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Outlier identification: PGLS analyses have demonstrated that human brain size represents a significant phylogenetic outlier compared to expectations based on primate scaling relationships, contradicting earlier non-phylogenetic claims that human brain size is only modestly enlarged
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Hominin trajectory mapping: PGLS has been used to characterize the evolutionary trajectory of exceptional hominin endocranial volume (ECV) relative to primate-wide brain-body mass scaling relationships
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Adaptive shift detection: By applying multi-optima Ornstein-Uhlenbeck models within a PGLS framework, researchers have identified shifts in the adaptive optima for brain size in the human lineage
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Neanderthal comparisons: PGLS analyses have suggested that larger brains provided fitness advantages that led to large brain sizes in both modern humans and Neanderthals
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Sex-specific analyses: PGLS has revealed insights about brain evolution by analyzing female-specific body mass data, which is more tightly linked to ecological and life-history factors than male data
These applications have fundamentally reshaped our understanding of human brain evolution by providing statistically rigorous comparative frameworks.
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What contradictions in human evolution research has PGLS helped resolve?
PGLS has helped resolve several important contradictions in human evolution research:
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Brain size expectations: PGLS resolved contradictory claims about human brain size, showing that when phylogeny is properly accounted for, human brain size is substantially larger than expected for a primate of human body mass, contradicting earlier claims of only 10% enlargement
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Scaling relationship accuracy: PGLS has addressed contradictions arising from non-phylogenetic methods that fail to incorporate trait co-variation resulting from shared evolutionary history
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Methodological inconsistencies: By providing a standardized statistical framework, PGLS has helped resolve contradictions that arose from different methodological approaches to analyzing comparative data
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Literature-based conflicts: The application of contradiction detection methods inspired by PGLS approaches has helped identify genuinely conflicting claims in the medical and evolutionary literature
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Hominin brain evolution timeline: PGLS has helped resolve contradictions regarding when exceptional brain enlargement occurred in the hominin lineage by providing a statistical framework for analyzing fossil evidence
These resolutions demonstrate how phylogenetically-informed methods can address seemingly contradictory findings that result from methodological rather than biological differences .
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Product Science Overview
6PGL is a cytosolic enzyme found in all organisms. In humans, it exists as a monomer composed of 258 amino acid residues with a molecular mass of approximately 30 kDa . The enzyme’s tertiary structure employs an α/β hydrolase fold, with active site residues clustered on the loops of the α-helices . The stability of the enzyme’s structure is reinforced through salt bridges between aspartic acid and arginine residues, as well as aromatic side-chain stacking interactions .
The hydrolysis reaction catalyzed by 6PGL proceeds via proton transfer to the O5 ring oxygen atom, similar to the mechanisms of xylose isomerase and ribose-5-phosphate isomerase . The reaction initiates with the attack of a hydroxide ion at the C5 ester, forming a tetrahedral intermediate. The elimination of the ester linkage follows, aided by the donation of a proton from an active site histidine residue . Molecular dynamic simulations have shown that the histidine residue is responsible for proton transfer, while arginine residues stabilize the negatively charged phosphate group .
6PGL plays a vital role in the PPP, which is responsible for producing ribulose 5-phosphate and NADPH. These products are essential for nucleotide synthesis and providing reducing equivalents for various biosynthetic reactions . The enzyme’s activity is crucial for maintaining cellular redox balance and supporting anabolic processes.
Recombinant 6PGL is produced using genetic engineering techniques, where the human gene encoding 6PGL is inserted into an expression vector and introduced into a host organism, such as bacteria or yeast. The host organism then expresses the human enzyme, which can be purified for research or therapeutic purposes.
