Target type: biologicalprocess
The process of assisting in the disassembly of non-covalent linkages in a protein or protein aggregate, often where the proteins are in a non-functional or denatured state. [GOC:mlg]
Protein unfolding, also known as denaturation, is a process where a protein loses its native three-dimensional structure and becomes a disordered polypeptide chain. This process can be triggered by various factors, including:
* **Temperature:** Increased temperature provides more energy to the protein, disrupting the weak bonds responsible for maintaining its structure.
* **pH:** Extreme pH values can disrupt the ionic interactions and hydrogen bonds within the protein, leading to unfolding.
* **Chemical agents:** Certain chemicals, such as urea and guanidine hydrochloride, can disrupt the hydrophobic interactions and hydrogen bonds within the protein, causing it to unfold.
* **Mechanical stress:** Physical forces, such as shaking or stirring, can also disrupt the protein structure.
The process of protein unfolding can be reversible or irreversible. Reversible unfolding occurs when the protein can regain its native structure after the denaturing agent is removed. Irreversible unfolding, on the other hand, results in permanent changes to the protein structure, rendering it inactive.
The unfolding process involves several steps:
1. **Initiation:** The protein begins to lose its native structure, with the weakest interactions being disrupted first.
2. **Propagation:** The unfolding process spreads throughout the protein, leading to the disruption of more bonds and the formation of disordered regions.
3. **Termination:** The protein reaches a fully unfolded state, where it is a disordered polypeptide chain.
The unfolding process can have significant consequences for the protein's function. Unfolded proteins can lose their ability to bind to substrates, catalyze reactions, or interact with other molecules. In some cases, unfolded proteins can even aggregate and form amyloid fibrils, which are associated with various diseases.
Understanding the process of protein unfolding is crucial for various fields, including biochemistry, molecular biology, and medicine. This knowledge can be used to design drugs that target specific protein structures, to develop techniques for protein purification and analysis, and to understand the mechanisms of disease development.
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| Protein | Definition | Taxonomy |
|---|---|---|
| Heat shock protein HSP 90-alpha | A heat shock protein HSP 90-alpha that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| n(6),n(6)-dimethyladenine | N(6),N(6)-dimethyladenine : A tertiary amine that is adenine substituted at N-6 by geminal methyl groups. | tertiary amine | |
| ns 1619 | NS 1619 : A member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one in which the hydrogens at positions 1 and 5 are replaced are replaced by 2-hydroxy-5-(trifluoromethyl)phenyl and trifluoromethyl groups, respectively. It is an opener/activator of the large-conductance calcium-activated potassium channel (Bkca). NS 1619: structure given in first source | (trifluoromethyl)benzenes; benzimidazoles; phenols | potassium channel opener |
| vorinostat | vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL). Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME. | dicarboxylic acid diamide; hydroxamic acid | antineoplastic agent; apoptosis inducer; EC 3.5.1.98 (histone deacetylase) inhibitor |
| adenosine diphosphate | Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. | adenosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | fundamental metabolite; human metabolite |
| 2-aminopyrimidine | aminopyrimidine : A member of the class of pyrimidines that is pyrimidine substituted by at least one amino group and its derivatives. pyrimidin-2-amine : An aminopyrimidine carrying an amino group at position 2. | aminopyrimidine | |
| 2-chloroadenosine | 5-chloroformycin A: structure given in first source | purine nucleoside | |
| indazoles | Indazoles: A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES. | indazole | |
| ethamivan | etamivan : Phenol substituted at C-2 and C-4 by a methoxy group and an N,N-diethylaminocarbonyl group respectively. A respiratory stimulant drug related to nikethamide, it has now fallen largely into disuse. ethamivan: minor descriptor (65-72); major descriptor (73-86); on-line search BENZAMIDES (66-86); INDEX MEDICUS search BENZAMIDES (65-72); ETHAMIVAN (73-86) | methoxybenzenes; phenols | |
| 9-fluorenone | fluoren-9-one : The simplest member of the class fluoren-9-ones that is 9H-fluorene bearing an oxo substituent at position 9. | fluoren-9-ones | fungal xenobiotic metabolite |
| alpha-aminopyridine | alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485 aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups. | ||
| silybin | silibinin : A flavonolignan isolated from milk thistle, Silybum marianum, that has been shown to exhibit antioxidant and antineoplastic activities. | aromatic ether; benzodioxine; flavonolignan; polyphenol; secondary alpha-hydroxy ketone | antineoplastic agent; antioxidant; hepatoprotective agent; plant metabolite |
| adenosine | quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| 4-aminopyrimidine | aminopyrimidine | ||
| 2-acetylamino-3-chloro-1,4-naphthoquinone | 2-acetylamino-3-chloro-1,4-naphthoquinone: structure in first source | ||
| 2-aminopyrazine | pyrazines | ||
| catalposide | |||
| adenosine-5'-carboxylic acid | purine nucleoside | ||
| hydroxybenzindazole | hydroxybenzindazole: structure | ||
| adenosine 5'-carboxamide | adenosine 5'-carboxamide: structure | ||
| 5-benzyloxytryptophan | |||
| isopentaquine | |||
| 5'-n-methylcarboxamideadenosine | 5'-N-methylcarboxamideadenosine: RN given refers to (beta-D)-isomer | ||
| n-methyladenosine | N-methyladenosine: is a inhibitor of cell differentiation N(6)-methyladenosine : A methyladenosine compound with one methyl group attached to N(6) of the adenine nucleobase. | methyladenosine | |
| deguelin | deguelin : A rotenone that is 13,13a-dihydro-3H-chromeno[3,4-b]pyrano[2,3-h]chromen-7(7aH)-one substituted by methoxy groups at positions 9 and 10, and by two methyl groups at position 3 (the 7aS,13aS-stereoisomer). It exists in abundant quantities in the bark, roots, and leaves of the Leguminosae family of plants and reported to exert anti-tumour effects in various cancers. deguelin: a natural product from Mundulea sericea; RN refers to (7aS-cis)-isomer; structure given in first source | aromatic ether; diether; organic heteropentacyclic compound; rotenones | angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; antiviral agent; apoptosis inducer; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; mitochondrial NADH:ubiquinone reductase inhibitor; plant metabolite |
| 2-(4-morpholinyl)-4h-1-benzopyran-4-one | 2-(4-morpholinyl)-4H-1-benzopyran-4-one: an aminochromone; exhibits both antiproliferative and antichemotactic activity in vitro | ||
| adenosine 5'-phosphoramidate | adenosine 5'-phosphoramidate : The phosphoramadite analogue of AMP. | organic phosphoramidate | Mycoplasma genitalium metabolite |
| adenosine-5'-(n-ethylcarboxamide) | Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity. N-ethyl-5'-carboxamidoadenosine : A derivative of adenosine in which the 5'-hydroxymethyl group is replaced by an N-ethylcarboxamido group. | adenosines; monocarboxylic acid amide | adenosine A1 receptor agonist; adenosine A2A receptor agonist; antineoplastic agent; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; vasodilator agent |
| 8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-pent-4-yn-1-yl-9H-purin-6-amine | 8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-pent-4-yn-1-yl-9H-purin-6-amine : A member of the class of 6-aminopurines that is 2-fluoroadenine carrying additional 2-chloro-3,4,5-trimethoxybenzyl and pent-4-yn-1-yl substituents at positions 8 and 9 respectively. | 6-aminopurines; acetylenic compound; methoxybenzenes; monochlorobenzenes; organofluorine compound | antineoplastic agent; Hsp90 inhibitor |
| cct018159 | CCT-018159 : A member of the class of pyrazoles that is 1H-pyrazole carrying 1,4-benzodioxane-6-yl and 5-ethyl-2,4-dihydroxyphenyl substituents at positions 4 and 5 respectively. CCT018159: structure in first source | benzodioxine; pyrazoles; resorcinols | antineoplastic agent; apoptosis inducer; Hsp90 inhibitor |
| adenosine-5'-(N-propyl)carboxamide | adenosine-5'-(N-propyl)carboxamide : A monocarboxylic acid amide that is the propyl amide of adenosine 5'-carboxylic acid. | adenosines; monocarboxylic acid amide | |
| ver-49009 | 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)pyrazole-3-carboxamide : An aromatic amide obtained by formal condensation of the carboxy group of 5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)pyrazole-3-carboxylic acid with the amino group of ethylamine. VER-49009: inhibits heat shock protein 90 molecular chaperone; structure in first source | aromatic amide; monochlorobenzenes; monomethoxybenzene; pyrazoles; resorcinols | Hsp90 inhibitor |
| geldanamycin | 1,4-benzoquinones; ansamycin; carbamate ester; organic heterobicyclic compound | antimicrobial agent; antineoplastic agent; antiviral agent; cysteine protease inhibitor; Hsp90 inhibitor | |
| 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin | 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: structure in first source alvespimycin : A 19-membered macrocyle that is geldanamycin in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group. | 1,4-benzoquinones; ansamycin; carbamate ester; secondary amino compound; tertiary amino compound | Hsp90 inhibitor |
| derrubone | derrubone: an inhibitor of the Hsp90 protein folding machinery from Derris robusta; structure in first source | isoflavanones | |
| monorden | monorden: inhibits HSP90 Heat-Shock Proteins, DNA topoisomerase VI and human Topoisomerase II | cyclic ketone; enone; epoxide; macrolide antibiotic; monochlorobenzenes; phenols | antifungal agent; metabolite; tyrosine kinase inhibitor |
| tanespimycin | CP 127374: analog of herbimycin A | 1,4-benzoquinones; ansamycin; carbamate ester; organic heterobicyclic compound; secondary amino compound | antineoplastic agent; apoptosis inducer; Hsp90 inhibitor |
| 1-aminoadenosine | 1-aminoadenosine: structure | ||
| 9h-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-n-(1-methylethyl)- | 9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-: an epichaperome (purine-scaffold) inhibitor; structure in first source | ||
| reblastatin | reblastatin: structure in first source | ||
| 5'-amino-5'-deoxyadenosine | |||
| gambogic acid | gambogic acid: RN given refers to (1R-(1alpha,1(Z),3abeta,5alpha,11beta,14aS*))-isomer | pyranoxanthones | metabolite |
| ipi 493 | 17-aminogeldanamycin: structure in first source | ||
| n-cyclopropyl adenosine-5'-carboxamide | |||
| ec 144 | EC 144: structure in first source | ||
| snx-7081 | SNX-7081: Anti-Inflammatory Agent; structure in first source | ||
| 6-o-coumaroylcatalpol | cinnamate ester | ||
| at 13387 | (2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone: structure in first source onalespib : A member of the class of isoindoles that is isoindole in which the amino group has been acylated by a 2,4-dihydroxy-5-isopropylbenzoyl group and in which position 5 of the isoidole moiety has been substituted by a (4-methylpiperazin-1-yl)methyl group. A second-generation Hsp90 inhibitor. | benzamides; isoindoles; N-alkylpiperazine; resorcinols; tertiary carboxamide | antineoplastic agent; Hsp90 inhibitor |
| cnf 2024 | 2-aminopurines; aromatic ether; organochlorine compound; pyridines | antineoplastic agent; Hsp90 inhibitor | |
| snx 2112 | SNX 2112: an orally available small molecule Hsp90 inhibitor; structure in first source | ||
| debio 0932 | CUDC 305: an Hsp90 inhibitor with antineoplastic activity; structure in first source | ||
| pf 04929113 | |||
| ch5164840 | CH5164840: biotin-labeled version of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) | ||
| novobiocin | novobiocin : A coumarin-derived antibiotic obtained from Streptomyces niveus. Novobiocin: An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189) | carbamate ester; ether; hexoside; hydroxycoumarin; monocarboxylic acid amide; monosaccharide derivative; phenols | antibacterial agent; antimicrobial agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Escherichia coli metabolite; hepatoprotective agent |
| tas-116 | |||
| 2-(3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2h-chromen-6-yl)ethanone | 2-(3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)ethanone: an Hsp90 inhibitor; structure in first source | ||
| ver-246608 | VER-246608: inhibits pyruvate dehydrogenase kinase; structure in first source | ||
| ver-50589 | VER-50589: inhibits heat shock protein 90 molecular chaperone; structure in first source | ||
| ver 52296 | luminespib : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxylic acid with the amino group of ethylamine. | aromatic amide; isoxazoles; monocarboxylic acid amide; morpholines; resorcinols | angiogenesis inhibitor; antineoplastic agent; Hsp90 inhibitor |
| sta 9090 | ring assembly; triazoles | ||
| nms-e973 | NMS-E973: structure in first source |