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heparan sulfate proteoglycan binding

Definition

Target type: molecularfunction

Binding to a heparan sulfate proteoglycan, any proteoglycan containing heparan sulfate as the glycosaminoglycan carbohydrate unit. [ISBN:0198506732]

Heparan sulfate proteoglycans (HSPGs) are a diverse family of molecules that play crucial roles in a wide range of biological processes, including cell signaling, adhesion, and migration. Their molecular function in binding is multifaceted and relies on the intricate interplay between their core protein and the attached heparan sulfate (HS) chains. These chains are highly sulfated, negatively charged polysaccharides that exhibit remarkable structural diversity. This diversity arises from the variations in sulfation patterns, chain length, and the presence of specific sugar modifications.

The binding of proteins to HSPGs is primarily mediated by the HS chains, which act as versatile molecular "glue" through electrostatic interactions. The highly negatively charged HS chains attract positively charged regions on proteins, termed "basic patches," facilitating their interaction. This interaction can be further refined by specific sugar modifications on the HS chains, creating a unique recognition code for different proteins.

**Key molecular functions of HSPG binding:**

* **Cell Signaling:** HSPGs act as co-receptors for various signaling molecules, such as growth factors, chemokines, and morphogens. They facilitate the formation of signaling complexes by concentrating these ligands at the cell surface, enhancing their local concentration and modulating their activity.
* **Adhesion:** HSPGs mediate cell-cell and cell-matrix interactions, contributing to cell adhesion and tissue organization. They can bind to various extracellular matrix components, including collagen, laminin, and fibronectin, as well as to other cell surface receptors, contributing to cell attachment and migration.
* **Regulation of Enzyme Activity:** HSPGs can modulate the activity of enzymes by acting as substrates, co-factors, or inhibitors. For instance, they can bind to and regulate the activity of proteases, enzymes involved in the degradation of proteins.
* **Development and Morphogenesis:** HSPGs play critical roles in developmental processes, including embryonic development, angiogenesis, and organogenesis. They influence cell migration, differentiation, and tissue patterning through their interactions with various signaling pathways.
* **Viral and Bacterial Infection:** HSPGs serve as receptors for certain viruses and bacteria, facilitating their entry into cells. This binding can initiate the infection process and contribute to the spread of these pathogens.

**Molecular Mechanisms of HSPG Binding:**

The molecular mechanisms of HSPG binding involve a complex interplay of electrostatic interactions, hydrogen bonding, and van der Waals forces. The negatively charged HS chains interact with positively charged amino acid residues on proteins, creating a stable binding interface. The specific sulfation pattern and the presence of certain sugar modifications on the HS chains can further fine-tune the binding affinity and specificity of the interaction.

In conclusion, the molecular function of heparan sulfate proteoglycan binding is multifaceted and encompasses diverse biological processes. Their ability to bind to a wide range of proteins, including growth factors, chemokines, and extracellular matrix components, positions them as crucial players in cell signaling, adhesion, development, and pathogenesis. The intricate structure and sulfation patterns of the HS chains provide a unique recognition code for specific proteins, enabling fine-tuning of their interactions and diverse biological roles.'
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Proteins (5)

ProteinDefinitionTaxonomy
Group IID secretory phospholipase A2A group IID secretory phospholipase A2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UNK4]Homo sapiens (human)
Receptor-type tyrosine-protein phosphatase SA receptor-type tyrosine-protein phosphatase S that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13332]Homo sapiens (human)
Integrin alpha-2An integrin alpha-2 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P17301]Homo sapiens (human)
Receptor-type tyrosine-protein phosphatase CA receptor-type tyrosine-protein phosphatase C that is encoded in the genome of human. [PRO:CNA, UniProtKB:P08575]Homo sapiens (human)
Lipoprotein lipaseA lipoprotein lipase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06858]Homo sapiens (human)

Compounds (20)

CompoundDefinitionClassesRoles
4-hydroxyphenylglyoxylic acid4-hydroxyphenylglyoxylate : Conjugate base of 4-hydroxyphenylglyoxylic acid.

4-hydroxyphenylglyoxylic acid: RN given refers to parent cpd
phenols
5-iodo-2-(oxaloamino)benzoic acidorganoiodine compound
9,10-phenanthrenequinone9,10-phenanthrenequinone: structurephenanthrenes
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
1,2-naphthoquinone1,2-naphthoquinone : The parent structure of the family of 1,2-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 2 of the naphthalene ring. It is a metabolite of naphthalene and is found in diesel exhaust particles.

naphthalene-1,2-dione: structure given in first source
1,2-naphthoquinonesaryl hydrocarbon receptor agonist;
carcinogenic agent
arginyl-glycyl-aspartyl-serinearginyl-glycyl-aspartyl-serine: corresponds to cell attachment site of fibronectin; located near carboxyl-terminal region of alpha-chain of fibrinogen; inhibits platelet aggregation & fibrinogen binding to activated platelets
3-octylthio-1,1,1-trifluoro-2-propanone3-octylthio-1,1,1-trifluoro-2-propanone: a pesticide synergist; inhibits juvenile hormone esterase
varespladibaromatic ether;
benzenes;
dicarboxylic acid monoamide;
indoles;
monocarboxylic acid;
primary carboxamide
anti-inflammatory drug;
antidote;
EC 3.1.1.4 (phospholipase A2) inhibitor
cryptotanshinonecryptotanshinone: from Salvia miltiorrhizaabietane diterpenoidanticoronaviral agent
2-(oxaloamino)benzoic acid(oxaloamino)benzoic acid
orlistatorlistat : A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.

Orlistat: A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.
beta-lactone;
carboxylic ester;
formamides;
L-leucine derivative
anti-obesity agent;
bacterial metabolite;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor
illudalic acidilludalic acid: isolated from Clitocybe illudens; structure in first source
baicaleintrihydroxyflavoneangiogenesis inhibitor;
anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 4.1.1.17 (ornithine decarboxylase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hormone antagonist;
plant metabolite;
prostaglandin antagonist;
radical scavenger
morinmorin : A pentahydroxyflavone that is 7-hydroxyflavonol bearing three additional hydroxy substituents at positions 2' 4' and 5.

morin: a light yellowish pigment found in the wood of old fustic (Chlorophora tinctoria)
7-hydroxyflavonol;
pentahydroxyflavone
angiogenesis modulating agent;
anti-inflammatory agent;
antibacterial agent;
antihypertensive agent;
antineoplastic agent;
antioxidant;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
hepatoprotective agent;
metabolite;
neuroprotective agent
scutellareinscutellarein : Flavone substituted with hydroxy groups at C-4', -5, -6 and -7.

scutellarein: aglycone of scutellarin from Scutellaria baicalensis; carthamidin is 2S isomer of scutellarein; do not confuse with isoscutellarein and/or isocarthamidin which are respective regioisomers, or with the scutelarin protein
tetrahydroxyflavonemetabolite
tricetintricetin : Flavone hydroxylated at positions 3', 4', 5, 5' and 7.pentahydroxyflavoneantineoplastic agent;
metabolite
indoxamindoxam: structure in first source
3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1h-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1h-indole-5-carboxylic acid3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid: an SHP2 inhibitor; structure in first source
variabilinvariabilin: an RGD-containing antagonist of glycoprotein IIb-IIIa from the hard tick, Dermacentor variabilis; amino acid sequence given in first source
xen445