https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Jason+TelfordProteopedia - User contributions [en]2026-09-15T23:05:42ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Ribonucleotide_Reductase&diff=3555199Ribonucleotide Reductase2022-05-02T18:26:15Z<p>Jason Telford: </p>
<hr />
<div>== Ribonucleotide Reductase ==<br />
<StructureSection load='1RLR' size='340' side='right' caption='Ribonucleotide Reductase' scene=''><br />
<br />
<br />
<br />
== Introduction ==<br />
<br />
Ribonucleotide reductase, <scene name='91/910568/1rlr_1/1'>RNR</scene>, is one of the major enzymes that aids in the synthesis of deoxyribonucleotides. These precursors of DNA are vital for DNA synthesis, so RNRs are required in all living cells to replicate and repair DNA. The reaction catalyzed through RNR is the only biochemical pathway that can synthesize new deoxyribonucleotide triphosphates (dNTPs).<ref name="intro">DOI:10.3389/fcimb.2014.00052</ref> This enzyme has led to and contributed to the evolution of genetic material that exists today. RNR consists of three different classes: I, II, and III. The classes differ in which they require different metal cofactors in order to initiate the reaction. This then leads to different environmental factors affecting the enzyme and its different classes. <br />
<br />
== Structure ==<br />
<br />
The structure of ribonucleotide reductase is composed of two components. One portion is the radical generator which produces and stores the radical. This portion is used to oxidize the substrate to its radical form which is the first step of the overall reaction. The second portion of the structure consists of a reductase. The reductase is the same for all three classes, but the radical generator differs. <ref name="structure">DOI:10.1016/S0079-6107(01)00014-1</ref> Class I ribonucleotide reductase produces the stable radical, <scene name='91/910568/Iron_center/2'>tyrosyl</scene>, through the dinuclear <scene name='91/910568/Iron_center/1'>iron center</scene> or <scene name='91/910568/Iron_center/4'>alternative iron center</scene> of the subunit. The three different classes of this enzyme have a cysteine residue that is located at the protein loop of the active site. Class II enzymes differ in which it uses cobalamin as a cofactor for the radical. The protein loop is in the center of the alpha, beta-barrel of the structural motif. The cysteine residue is conserved until it is converted to a thiyl radical. The conversion to the thiyl radical is needed to initiate substrate turnover. The different classes of RNR are different but do show some similarities which suggest that they all evolved from one common reductase. <ref name="pubmed">DOI:10.1016/j.bbapap.2004.02.007</ref> Class III of RNR is comprised of two proteins that require an iron-sulfur center. <br />
<br />
== Function ==<br />
<br />
The conversion from ribonucleotides to deoxyribonucleotides is a radically-based reaction. Organic free radicals are stored by RNR until they are needed for catalysis. Class I is the most studied and most well known enzyme that is a part of the RNR family. It is composed of two subunits, alpha and beta, that are homodimeric. The alpha subunit contains the active site and two allosteric sites. The active site contains a catalytic subunit, and the allosteric sites are used for regulation, enzyme activity, and substrate specificity. The beta portion contains the metal cofactor that initiates reduction. Class I is subdivided into three more enzymes that are class Ia, Ib, and Ic. Class one is split even further because it is depending on the specific type of metal center that is needed for protein radical. All three classes share the same function for the beta subunit which is synthesizing the radical which is transferred using a radical transfer pathway. Class Ia requires a di-iron center as the nrdAB gene codes for this enzyme. Class Ib uses either a di-manganese center or a di-ferric center. This specific class differs from the other class I enzymes by lacking the active site located at the N-terminal portion of the protein. This enzyme is coded by the gene nrdHIEF Class Ic is encoded by the nrdAB gene, and it requires a manganese-iron center. Class I and its subdivision are all aerobic and require oxygen for the generation of the radical. This enzyme can be found in eukaryotes, archaea, eubacteria, and bacteriophages. Class II is encoded by the nrdj gene that harbors the allosteric sites and active site of the enzyme, so the enzyme itself only contains one subunit which is alpha or alpha2. There is an allosteric specificity site, but no allosteric active site. S-adenosylcobalamin is used as a cofactor in order to generate the cysteinyl radical. <ref name="intro">DOI:10.3389/fcimb.2014.00052</ref> The radical is formed when the bond between the adenosyl and cobalamin is cleaved. It has been recently discovered that several class II RNRs with catalytic domains of the B12-dependent enzyme are related to class I and III RNRs. The reaction for class II can be aerobic or anaerobic because it is oxygen independent. This class is found in archaea, eubacteria, and bacteriophages. It is most studied in microorganisms such as Lactobacillus leichmannii. Class III is composed of two proteins that are homodimeric. It is encoded by nrdG and nrdD genes which contain a large catalytic subunit with an active site and two allosteric sites used for regulation. The NrdG protein, activase, initiates the generation of the radical which requires binding of the iron-sulfur cluster in the center of the protein with S-adenosylmethionine. The interaction between the metal center and adenosylmethionine synthesizes a glycyl radical which causes this reaction to be completely anaerobic. The glycyl radical forms at the C-terminal of the protein which is sensitive to oxygen. <ref name="intro">DOI:10.3389/fcimb.2014.00052</ref> Along with that and the potential of the metal center oxidizing, this reaction cannot run in the presence of oxygen. This class is found in bacteriophages, eubacteria, and archaea. <br />
<br />
== Disease ==<br />
<br />
Activity of RNR is controlled by substrate specificity and enzymatic activity. Substrate activity functions by allowing the binding of different nucleotides which results in the reduction of a specific NTP. This regulation occurs at the active site. ATP or dATP can bind to activate or inhibit activity which allows for enzymatic activity to be controlled. Mutations can occur within the genome if there is an imbalance in the pools of dNTPs. These are the building blocks for DNA, and if the pool is altered, then it can lead to genomic instability. <ref name="disease">DOI:10.1038/onc.2014.155</ref> Having accurate DNA repair and replication allows for development, tumor-free cells, and growth. Having issues within the genome can cause several human diseases, mitochondrial disorders, and cause a person to be more susceptible to infection and cancer. High expressions of RNR is a main characteristic for cancers since it influences DNA replication so heavily. For this reason, RNRs play a major role in targeting anticancer and antibacterial drugs and therapies. RNR inhibitors are being studied to see if they can potentially serve as cancer treatment that is effective. More and more research is being done everyday in order to fully understand ribonucleotide reductase and all of its classes. For decades, dNTP machinery and RNR has been used and exploited for therapeutic benefits. They serve an important target for developing an efficient cancer drug. <br />
<br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=(1%E2%86%923)-%CE%B1-Glucanases:_An_Alternative_to_Control_Dental_Plaque_and_Improve_Oral_Health&diff=3555178(1→3)-α-Glucanases: An Alternative to Control Dental Plaque and Improve Oral Health2022-05-02T17:56:28Z<p>Jason Telford: </p>
<hr />
<div>==(1→3)-α-Glucanases==<br />
==Structures of Biofilm Forming Enzymes==<br />
<StructureSection load='7C7D' size='340' side='right' caption='' scene=''><br />
<br />
<br />
== Introduction ==<br />
Dental plaque is the accumulation of biofilm, a collection of various microbial species that colonize the surfaces of our teeth. This diverse set of microorganisms include things like bacteria and fungi, and believe it or not, it is actually perfectly normal and even advantageous to have these things living inside our mouths. This is because some of the microorganisms that make up our biofilm are considered favorable or “good” in that they prevent colonization of things like the “bad,” not so favorable microorganisms – an idea of commensalism that helps us defend ourselves against harmful, infectious microbial species. Although at times beneficial to our oral health, some of the microorganisms that live within these oral biofilms can, if given the opportunity to, over grow within the mouth and become pathogenic, having the ability to damage the teeth and gums and potentially cause an oral infection and/or disease. This is why dental plaque control is extremely important to not only our oral health, but systemic health too. The question is, however, if we want to figure out how to control the formation of dental plaque, we need to understand how biofilms are made. Only then can we begin to find an alternative to fight against its accumulation and prevent oral disease. <br />
<br />
One of the many contributing factors to the formation of dental plaque is complex, extracellular sugars such as (1→3)-α-glucans produced by bacterial and fungal species living and growing inside the mouth. (1→3)-α-glucans are insoluble, linear α-1,3-linked homopolymers of D-glucose that play a key role in the structure and function of the biofilm matrix. (1→3)-α-glucans possess (1→3)-α-glycosidic bonds and hydrogen bonds that provide the sugar with rigidity and water insolubility, respectively. This not only allows (1→3)-α-glucans to remain undissolved in the oral cavity, but it also helps them resist being washed away with oral fluids <ref name="A">D.A.Rees, W.E. Scott. Polysaccharide conformation. Part VI. Computer model-building for linear and branched pyranoglycans. Correlations with biological function. Preliminary assessment of inter-residue forces in aqueous solution. Further interpretation of optical rotation in terms of chain conformation. Journal of the Chemical Society B: Physical Organic. 1971:469–479 [https://doi.org/10.1039/j29710000469 DOI:10.1039/j29710000469]</ref>. The (1→3)-α-glycosidic bonds of (1→3)-α-glucans are also resistant to enzymes naturally present in the oral cavity, and this enables the sugar to form and maintain a stable, durable biofilm matrix that can accumulate around the teeth as dental plaque <ref name="B">Eifuku H, Yoshimitsu-Narita A, Sato S, Yakushiji T, Inoue M. Production and partial characterization of the extracellular polysaccharides from oral streptococcus salivarius. Carbohydrate Research. 1989;194:247–260. [https://doi.org/10.1016/0008-6215(89)85023-2 DOI:10.1016/0008-6215(89)85023-2]</ref><ref name="C">DOI:10.1159/000259783</ref>. However, there are enzymes, known as (1→3)-α-glucanases, that can be introduced into the oral cavity to specifically target and break down these sugars. (1→3)-α-glucanases are a type of glycosidase, or glycoside hydrolase, meaning that they work by catalyzing the hydrolysis of the (1→3)-α-glycosidic bonds in (1→3)-α-glucans. Knowing their function, we can use these hydrolytic enzymes in oral hygiene products, such as toothpaste and mouthwashes, to fight against bacterial and fungal (1→3)-α-glucans and the sugars’ contribution to the structure and function of the biofilm matrix. Perhaps introducing these enzymes to the oral cavity would essentially reduce the formation of dental plaque, and therefore, prevent the development of infectious oral diseases.<br />
<br />
== Molecular Biology of (1→3)-α-Glucanases ==<br />
Unlike other glycoside hydrolases such as amylases, cellulases, chitinases, and even β-glucanases for that matter, there is not much biochemical and structural information on (1→3)-α-glucanases. For the most part, (1→3)-α-glucanases are generally known; however, we do not have enough information on the enzymes to understand the specifics. Although this makes it more difficult for us to thoroughly explore the enzymes’ structural components such as shape, what residues make up the active site, as well as additional residues or cofactors that may be significant to the enzymes’ stability or mode of action, we do have some basic knowledge on the molecular biology of (1→3)-α-glucanases. <br />
<br />
(1→3)-α-glucanases are naturally produced by various fungal and bacterial species. For this reason, (1→3)-α-glucanases can be classified into two families of glycoside hydrolases, GH-71 and GH-87. Although this classification was originally made based on differences in amino acid sequence, the two families differentiate between which microbial species the enzymes are from. While GH-71 (1→3)-α-glucanases belong to a family of enzymes found in fungal species (1→3)-α-glucans, GH-87 (1→3)-α-glucanases are those that are made by bacteria. The two families also differ in molecular weights, a finding that has been determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS/PAGE). While fungal enzymes range from a limited 67-90 kDa, bacterial enzymes vary from a much larger range of 48-160 kDa. Most (1→3)-α-glucanases, regardless of family origin, have been identified as monomeric proteins; however, there have been reports suggesting that the enzymes could also be dimers or even tetramers <ref name="D">DOI:10.1016/j.ijbiomac.2015.05.052</ref>.<br />
<br />
With the use of nucleotide and amino acid sequencing, bacterial and fungal genes that encode proteins with (1→3)-α-glucanase activity have been identified. Based on these analyses, both bacterial and fungal genes show significant sequence identity, sharing high homology among strains of the same species. In bacterial enzymes, (1→3)-α-glucanases have a C-terminal domain that is considered the catalytic domain, as this domain holds the primary glucanase activity. The N-terminal domain, in contrast, is more supportive in that it contains additional supplementary modules that are involved in substrate binding. Although this kind of organization is also found in fungal (1→3)-α-glucanases, the terminal domains of these enzymes differ in responsibility. In fact, functions of the terminal domains found in fungal (1→3)-α-glucanases are quite opposite from those of bacterial enzymes. In fungal (1→3)-α-glucanases, the C-terminal domain rather functions as the substrate binding domain while the N-terminal domain is the catalytic domain. This is because, unlike in bacterial (1→3)-α-glucanases, the C-terminal domain is what targets the enzyme to the sugar substrate and the N-terminal domain, on the other hand, works by enzymatically cleaving the glycosidic bonds <ref name="D"/>.<br />
<br />
== Characterization of (1→3)-α-Glucanases ==<br />
Numerous (1→3)-α-glucanases have been purified and characterized, giving us insight into their catalytic behavior and stability when exposed to certain temperature and pH conditions. Through extensive experimentation, the optimal temperature for both bacterial and fungal (1→3)-α-glucanases was found to range from 40 to 56 ℃. However, when it comes to optimal pH, the two families differ quite drastically. While fungal enzymes have increased activity in acidic environments with a pH range of 4.5 to 5.5, bacterial enzymes work best in a more neutral environment with slightly higher pH values of 5.5 to 6.9. This is because fungal (1→3)-α-glucanases are only stable at a limited pH range of 5.0 to 7.0, whereas bacterial (1→3)-α-glucanases maintain stability at a much larger pH range that includes alkaline conditions, ranging from 4.0 to 11.0 <ref name="D"/>. <br />
<br />
All (1→3)-α-glucanases function as glycoside hydrolases that break down the glycosidic bonds of (1→3)-α-glucans. Some of these enzymes are thought to function through a processive mechanism, meaning that they remain attached to their substrate, in this case (1→3)-α-glucans, and repetitively catalyze the hydrolysis of the sugar’s glycosidic bonds before dissociating <ref name="E">W.A. Breyer, B.W. Matthews. A structural basis for processivity. Protein Science. 2001;10(9):1699–1711 [https://doi.org/10.1110/ps.10301 DOI:10.1110/ps.10301]</ref>. However, the way that these enzymes go about doing so can be different from one another in terms of starting point of hydrolysis and what products are released. We differentiate between these modes of action by organizing (1→3)-α-glucanases into two distinct groups, ''exo''-(1→3)-α-glucanases and ''endo''-(1→3)-α-glucanases. ''Exo''-(1→3)-α-glucanases hydrolyze terminal (1→3)-α-glucoside linkages at non-reducing ends and release monosaccharides and disaccharides. In contrast, ''endo''-(1→3)-α-glucanases hydrolyze internal (1→3)-α-glucoside linkages at random sites and release nigerooligosaccharides. Although the ''exo''-(1→3)-α-glucanases and ''endo''-(1→3)-α-glucanases act at different locations on the (1→3)-α-glucan chain and release varying products, their catalytic function is the same in that they both hydrolyze the (1→3)-α-glycosidic bonds of (1→3)-α-glucans, perhaps through a processive mechanism <ref name="D"/>. <br />
<br />
Additionally, all (1→3)-α-glucanases have a high specificity for their substrate, (1→3)-α-glycosidic linkages, making them extremely effective in catalyzing the degradation of (1→3)-α-glucan sugars. In fact, some of these enzymes even hydrolyze (1→3)-α-glucan sugars that include other linkages such as (1→4)-α-linkages and (1→6)-α-linkages in addition to (1→3)-α-linkages. This means that (1→3)-α-glucanases can not only break down linear (1→3)-α-glucans, but also branched (1→3)-α-glucans, as both forms of these sugars include their (1→3)-α-glycosidic linkage substrate <ref name="F">DOI:10.1007/s10529-007-9311-z</ref><ref name="G">Wiater A, Szczodrak J, Rogalski J. Hydrolysis of mutan and prevention of its formation in streptococcal films by fungal α-D-Glucanases. Process Biochemistry. 2004;39(11):1481–1489 [https://doi.org/10.1016/s0032-9592(03)00281-4 DOI:10.1016/s0032-9592(03)00281-4]</ref>.<br />
<br />
== Examples of (1→3)-α-Glucanases ==<br />
Again, (1→3)-α-glucanas are extracellular sugars that can be made by bacteria or fungi, which explains why there are (1→3)-α-glucanases for both families. Let us look at a (1→3)-α-glucanase from a ''Streptococcus'' species, ''Streptomyces thermodiastaticus'' strain HF3-3 (Agl-ST). Since this is a bacterial species, the (1→3)-α-glucanase has been identified as a glycoside hydrolase family 87 (GH87). This particular enzyme is also classified as an ''endo''-(1→3)-α-glucanases, as it specifically hydrolyzes ''Streptococcal'' (1→3)-α-glucans’ internal glycosidic bonds at random sites along the chain. The enzyme has a sequence length of 610 and is considered a dimer, having its structure consist of two protein domains. Its monomeric <scene name='91/911195/Agl-st_catalytic_unit/4'>catalytic unit</scene> weighs 126.87 kDa and is one single protein chain composed of two modules, a <scene name='91/911195/B-sandwich_of_agl-st/1'>β-sandwich fold module</scene> and a <scene name='91/911195/B-helix_of_agl-st/1'>right-handed β-helix fold module</scene> <ref name="H">DOI:10.1016/j.bbrc.2020.09.133</ref>. <br />
<br />
This type of structure is also found in another (1→3)-α-glucanase member from the glycoside hydrolase family 87 (GH87), ''Paenibacillus glycanilyticus'' strain FH11 (Agl-FH1) - with moderate sequence identities between each other (approximately 27% between the catalytic units) <ref name="H"/>. Just as in ''Streptomyces thermodiastaticus'' strain HF3-3, ''Paenibacillus glycanilyticus'' strain FH11 hydrolyzes ''Streptococcal'' (1→3)-α-glucans’ glycosidic bonds with an ''endo'' mode of action. In contrast, this enzyme only consists of one single protein chain, making it a monomer with a shorter sequence length of 573. This makes sense as to why its catalytic domain is also much smaller in size, only weighing 63.33 kDa. The crystal structure of this enzyme has been identified, revealing the Agl-FH1 <scene name='91/911195/Agl-fh1_catalytic_domain/1'>catalytic domain</scene> to resemble that of Agl-ST, also being made up of two modules, the <scene name='91/911195/B-sandwich_of_agl-fh1/1'>β-sandwich fold module</scene> and the <scene name='91/911195/B-helix_of_agl-fh1/1'>right-handed β-helix fold module</scene> <ref name="I">DOI:10.1111/febs.15161</ref>.<br />
<br />
== Conclusion ==<br />
Since sugars such as (1→3)-α-glucans are a primary component of the biofilm matrix and partly responsible for the formation of dental plaque, it makes them potential targets for antimicrobial agents. By including the hydrolytic enzymes (1→3)-α-glucanases into oral hygiene products, like toothpaste and mouthwashes, we have the opportunity to compromise the structural integrity and function of the biofilm matrix. This is because introducing these enzymes into the oral cavity would break down bacterial and fungal (1→3)-α-glucans by catalyzing the hydrolysis of their glycosidic bonds. This would essentially make the formation of dental plaque a more difficult task for bacteria and fungi that produce these sugars, and therefore, prevent the development of infectious oral diseases such as dental caries and gum disease. Not to mention, using enzymes like (1→3)-α-glucanases as an alternative to mechanically clean our mouths is hopeful and beneficial because, unlike most antiseptics, they are substrate specific. (1→3)-α-glucanases only target the (1→3)-α-glycosidic bonds of bacterial and fungal (1→3)-α-glucans, known components of the biofilm matrix, while disregarding other things like commensal microorganisms. Other antimicrobials that are used in our oral hygiene products, like alcohol for example, do not discriminate like this - they inhibit the bad microorganisms as well as the good microorganisms that are necessary to maintain our normal oral microbiota, giving them the potential to disrupt our natural balance of microorganisms in the mouth. This is why (1→3)-α-glucanases could be used as an alternative to control dental plaque and the development of infectious oral diseases, helping us maintain and improve our overall oral health.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=(1%E2%86%923)-%CE%B1-Glucanases:_An_Alternative_to_Control_Dental_Plaque_and_Improve_Oral_Health&diff=3555176(1→3)-α-Glucanases: An Alternative to Control Dental Plaque and Improve Oral Health2022-05-02T17:55:24Z<p>Jason Telford: </p>
<hr />
<div>==(1→3)-α-Glucanases==<br />
==Biofilm formation==<br />
<StructureSection load='7C7D' size='340' side='right' caption='' scene=''><br />
<br />
<br />
== Introduction ==<br />
Dental plaque is the accumulation of biofilm, a collection of various microbial species that colonize the surfaces of our teeth. This diverse set of microorganisms include things like bacteria and fungi, and believe it or not, it is actually perfectly normal and even advantageous to have these things living inside our mouths. This is because some of the microorganisms that make up our biofilm are considered favorable or “good” in that they prevent colonization of things like the “bad,” not so favorable microorganisms – an idea of commensalism that helps us defend ourselves against harmful, infectious microbial species. Although at times beneficial to our oral health, some of the microorganisms that live within these oral biofilms can, if given the opportunity to, over grow within the mouth and become pathogenic, having the ability to damage the teeth and gums and potentially cause an oral infection and/or disease. This is why dental plaque control is extremely important to not only our oral health, but systemic health too. The question is, however, if we want to figure out how to control the formation of dental plaque, we need to understand how biofilms are made. Only then can we begin to find an alternative to fight against its accumulation and prevent oral disease. <br />
<br />
One of the many contributing factors to the formation of dental plaque is complex, extracellular sugars such as (1→3)-α-glucans produced by bacterial and fungal species living and growing inside the mouth. (1→3)-α-glucans are insoluble, linear α-1,3-linked homopolymers of D-glucose that play a key role in the structure and function of the biofilm matrix. (1→3)-α-glucans possess (1→3)-α-glycosidic bonds and hydrogen bonds that provide the sugar with rigidity and water insolubility, respectively. This not only allows (1→3)-α-glucans to remain undissolved in the oral cavity, but it also helps them resist being washed away with oral fluids <ref name="A">D.A.Rees, W.E. Scott. Polysaccharide conformation. Part VI. Computer model-building for linear and branched pyranoglycans. Correlations with biological function. Preliminary assessment of inter-residue forces in aqueous solution. Further interpretation of optical rotation in terms of chain conformation. Journal of the Chemical Society B: Physical Organic. 1971:469–479 [https://doi.org/10.1039/j29710000469 DOI:10.1039/j29710000469]</ref>. The (1→3)-α-glycosidic bonds of (1→3)-α-glucans are also resistant to enzymes naturally present in the oral cavity, and this enables the sugar to form and maintain a stable, durable biofilm matrix that can accumulate around the teeth as dental plaque <ref name="B">Eifuku H, Yoshimitsu-Narita A, Sato S, Yakushiji T, Inoue M. Production and partial characterization of the extracellular polysaccharides from oral streptococcus salivarius. Carbohydrate Research. 1989;194:247–260. [https://doi.org/10.1016/0008-6215(89)85023-2 DOI:10.1016/0008-6215(89)85023-2]</ref><ref name="C">DOI:10.1159/000259783</ref>. However, there are enzymes, known as (1→3)-α-glucanases, that can be introduced into the oral cavity to specifically target and break down these sugars. (1→3)-α-glucanases are a type of glycosidase, or glycoside hydrolase, meaning that they work by catalyzing the hydrolysis of the (1→3)-α-glycosidic bonds in (1→3)-α-glucans. Knowing their function, we can use these hydrolytic enzymes in oral hygiene products, such as toothpaste and mouthwashes, to fight against bacterial and fungal (1→3)-α-glucans and the sugars’ contribution to the structure and function of the biofilm matrix. Perhaps introducing these enzymes to the oral cavity would essentially reduce the formation of dental plaque, and therefore, prevent the development of infectious oral diseases.<br />
<br />
== Molecular Biology of (1→3)-α-Glucanases ==<br />
Unlike other glycoside hydrolases such as amylases, cellulases, chitinases, and even β-glucanases for that matter, there is not much biochemical and structural information on (1→3)-α-glucanases. For the most part, (1→3)-α-glucanases are generally known; however, we do not have enough information on the enzymes to understand the specifics. Although this makes it more difficult for us to thoroughly explore the enzymes’ structural components such as shape, what residues make up the active site, as well as additional residues or cofactors that may be significant to the enzymes’ stability or mode of action, we do have some basic knowledge on the molecular biology of (1→3)-α-glucanases. <br />
<br />
(1→3)-α-glucanases are naturally produced by various fungal and bacterial species. For this reason, (1→3)-α-glucanases can be classified into two families of glycoside hydrolases, GH-71 and GH-87. Although this classification was originally made based on differences in amino acid sequence, the two families differentiate between which microbial species the enzymes are from. While GH-71 (1→3)-α-glucanases belong to a family of enzymes found in fungal species (1→3)-α-glucans, GH-87 (1→3)-α-glucanases are those that are made by bacteria. The two families also differ in molecular weights, a finding that has been determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS/PAGE). While fungal enzymes range from a limited 67-90 kDa, bacterial enzymes vary from a much larger range of 48-160 kDa. Most (1→3)-α-glucanases, regardless of family origin, have been identified as monomeric proteins; however, there have been reports suggesting that the enzymes could also be dimers or even tetramers <ref name="D">DOI:10.1016/j.ijbiomac.2015.05.052</ref>.<br />
<br />
With the use of nucleotide and amino acid sequencing, bacterial and fungal genes that encode proteins with (1→3)-α-glucanase activity have been identified. Based on these analyses, both bacterial and fungal genes show significant sequence identity, sharing high homology among strains of the same species. In bacterial enzymes, (1→3)-α-glucanases have a C-terminal domain that is considered the catalytic domain, as this domain holds the primary glucanase activity. The N-terminal domain, in contrast, is more supportive in that it contains additional supplementary modules that are involved in substrate binding. Although this kind of organization is also found in fungal (1→3)-α-glucanases, the terminal domains of these enzymes differ in responsibility. In fact, functions of the terminal domains found in fungal (1→3)-α-glucanases are quite opposite from those of bacterial enzymes. In fungal (1→3)-α-glucanases, the C-terminal domain rather functions as the substrate binding domain while the N-terminal domain is the catalytic domain. This is because, unlike in bacterial (1→3)-α-glucanases, the C-terminal domain is what targets the enzyme to the sugar substrate and the N-terminal domain, on the other hand, works by enzymatically cleaving the glycosidic bonds <ref name="D"/>.<br />
<br />
== Characterization of (1→3)-α-Glucanases ==<br />
Numerous (1→3)-α-glucanases have been purified and characterized, giving us insight into their catalytic behavior and stability when exposed to certain temperature and pH conditions. Through extensive experimentation, the optimal temperature for both bacterial and fungal (1→3)-α-glucanases was found to range from 40 to 56 ℃. However, when it comes to optimal pH, the two families differ quite drastically. While fungal enzymes have increased activity in acidic environments with a pH range of 4.5 to 5.5, bacterial enzymes work best in a more neutral environment with slightly higher pH values of 5.5 to 6.9. This is because fungal (1→3)-α-glucanases are only stable at a limited pH range of 5.0 to 7.0, whereas bacterial (1→3)-α-glucanases maintain stability at a much larger pH range that includes alkaline conditions, ranging from 4.0 to 11.0 <ref name="D"/>. <br />
<br />
All (1→3)-α-glucanases function as glycoside hydrolases that break down the glycosidic bonds of (1→3)-α-glucans. Some of these enzymes are thought to function through a processive mechanism, meaning that they remain attached to their substrate, in this case (1→3)-α-glucans, and repetitively catalyze the hydrolysis of the sugar’s glycosidic bonds before dissociating <ref name="E">W.A. Breyer, B.W. Matthews. A structural basis for processivity. Protein Science. 2001;10(9):1699–1711 [https://doi.org/10.1110/ps.10301 DOI:10.1110/ps.10301]</ref>. However, the way that these enzymes go about doing so can be different from one another in terms of starting point of hydrolysis and what products are released. We differentiate between these modes of action by organizing (1→3)-α-glucanases into two distinct groups, ''exo''-(1→3)-α-glucanases and ''endo''-(1→3)-α-glucanases. ''Exo''-(1→3)-α-glucanases hydrolyze terminal (1→3)-α-glucoside linkages at non-reducing ends and release monosaccharides and disaccharides. In contrast, ''endo''-(1→3)-α-glucanases hydrolyze internal (1→3)-α-glucoside linkages at random sites and release nigerooligosaccharides. Although the ''exo''-(1→3)-α-glucanases and ''endo''-(1→3)-α-glucanases act at different locations on the (1→3)-α-glucan chain and release varying products, their catalytic function is the same in that they both hydrolyze the (1→3)-α-glycosidic bonds of (1→3)-α-glucans, perhaps through a processive mechanism <ref name="D"/>. <br />
<br />
Additionally, all (1→3)-α-glucanases have a high specificity for their substrate, (1→3)-α-glycosidic linkages, making them extremely effective in catalyzing the degradation of (1→3)-α-glucan sugars. In fact, some of these enzymes even hydrolyze (1→3)-α-glucan sugars that include other linkages such as (1→4)-α-linkages and (1→6)-α-linkages in addition to (1→3)-α-linkages. This means that (1→3)-α-glucanases can not only break down linear (1→3)-α-glucans, but also branched (1→3)-α-glucans, as both forms of these sugars include their (1→3)-α-glycosidic linkage substrate <ref name="F">DOI:10.1007/s10529-007-9311-z</ref><ref name="G">Wiater A, Szczodrak J, Rogalski J. Hydrolysis of mutan and prevention of its formation in streptococcal films by fungal α-D-Glucanases. Process Biochemistry. 2004;39(11):1481–1489 [https://doi.org/10.1016/s0032-9592(03)00281-4 DOI:10.1016/s0032-9592(03)00281-4]</ref>.<br />
<br />
== Examples of (1→3)-α-Glucanases ==<br />
Again, (1→3)-α-glucanas are extracellular sugars that can be made by bacteria or fungi, which explains why there are (1→3)-α-glucanases for both families. Let us look at a (1→3)-α-glucanase from a ''Streptococcus'' species, ''Streptomyces thermodiastaticus'' strain HF3-3 (Agl-ST). Since this is a bacterial species, the (1→3)-α-glucanase has been identified as a glycoside hydrolase family 87 (GH87). This particular enzyme is also classified as an ''endo''-(1→3)-α-glucanases, as it specifically hydrolyzes ''Streptococcal'' (1→3)-α-glucans’ internal glycosidic bonds at random sites along the chain. The enzyme has a sequence length of 610 and is considered a dimer, having its structure consist of two protein domains. Its monomeric <scene name='91/911195/Agl-st_catalytic_unit/4'>catalytic unit</scene> weighs 126.87 kDa and is one single protein chain composed of two modules, a <scene name='91/911195/B-sandwich_of_agl-st/1'>β-sandwich fold module</scene> and a <scene name='91/911195/B-helix_of_agl-st/1'>right-handed β-helix fold module</scene> <ref name="H">DOI:10.1016/j.bbrc.2020.09.133</ref>. <br />
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This type of structure is also found in another (1→3)-α-glucanase member from the glycoside hydrolase family 87 (GH87), ''Paenibacillus glycanilyticus'' strain FH11 (Agl-FH1) - with moderate sequence identities between each other (approximately 27% between the catalytic units) <ref name="H"/>. Just as in ''Streptomyces thermodiastaticus'' strain HF3-3, ''Paenibacillus glycanilyticus'' strain FH11 hydrolyzes ''Streptococcal'' (1→3)-α-glucans’ glycosidic bonds with an ''endo'' mode of action. In contrast, this enzyme only consists of one single protein chain, making it a monomer with a shorter sequence length of 573. This makes sense as to why its catalytic domain is also much smaller in size, only weighing 63.33 kDa. The crystal structure of this enzyme has been identified, revealing the Agl-FH1 <scene name='91/911195/Agl-fh1_catalytic_domain/1'>catalytic domain</scene> to resemble that of Agl-ST, also being made up of two modules, the <scene name='91/911195/B-sandwich_of_agl-fh1/1'>β-sandwich fold module</scene> and the <scene name='91/911195/B-helix_of_agl-fh1/1'>right-handed β-helix fold module</scene> <ref name="I">DOI:10.1111/febs.15161</ref>.<br />
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== Conclusion ==<br />
Since sugars such as (1→3)-α-glucans are a primary component of the biofilm matrix and partly responsible for the formation of dental plaque, it makes them potential targets for antimicrobial agents. By including the hydrolytic enzymes (1→3)-α-glucanases into oral hygiene products, like toothpaste and mouthwashes, we have the opportunity to compromise the structural integrity and function of the biofilm matrix. This is because introducing these enzymes into the oral cavity would break down bacterial and fungal (1→3)-α-glucans by catalyzing the hydrolysis of their glycosidic bonds. This would essentially make the formation of dental plaque a more difficult task for bacteria and fungi that produce these sugars, and therefore, prevent the development of infectious oral diseases such as dental caries and gum disease. Not to mention, using enzymes like (1→3)-α-glucanases as an alternative to mechanically clean our mouths is hopeful and beneficial because, unlike most antiseptics, they are substrate specific. (1→3)-α-glucanases only target the (1→3)-α-glycosidic bonds of bacterial and fungal (1→3)-α-glucans, known components of the biofilm matrix, while disregarding other things like commensal microorganisms. Other antimicrobials that are used in our oral hygiene products, like alcohol for example, do not discriminate like this - they inhibit the bad microorganisms as well as the good microorganisms that are necessary to maintain our normal oral microbiota, giving them the potential to disrupt our natural balance of microorganisms in the mouth. This is why (1→3)-α-glucanases could be used as an alternative to control dental plaque and the development of infectious oral diseases, helping us maintain and improve our overall oral health.<br />
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</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=Constans&diff=3555068Constans2022-05-02T15:55:19Z<p>Jason Telford: </p>
<hr />
<div>==Structural highlights: CONSTANS CO==<br />
<StructureSection load='7VSQ ' size='340' side='right'caption='[[7VSQ]], [[Resolution|resolution]] 1.68&Aring;' scene=''><br />
Constans (CO) is is a Zinc finger containing a domain known as B-boxes. Cysteine and histidine coordinate zinc. Mutations identified within the residues resulted in late flowering which is disadvantageous to reproduction patterns, and suggests they are highly conserved. B-boxes are involved in protein-protein interactions. The C-terminal contains 40 main amino acids (C-terminal contains 70-80 in entirety). In arabidopsis, 32 B-box transcription proteins have been identified thus far. CO, which is considered a BBX1, activates the expression of FT by binding to the CORE1 and CORE2 of the FT promoter. Each B-box transcription protein serves to regulate flowering by stimulating or repressing FT hormone. BBX28 is known to decrease FT transcription, specifically in the late afternoons and dark periods. BBX28 is able to interact with CO through the N-terminus. This works by decreasing recruitment of CO to the FT locus. Constans-like genes (COLs) are very genetically related homologs to Constans (CO). Specifically, CO1 has a greater than 80% amino acid genetic similarity to CO. While identity is similar, function of CO1 varies among identified organisms. <br />
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== Function ==<br />
As flowers serve as the reproductive structure of all Angiosperms, the regulation of flowering plants is crucial in a plant’s survival and viability. CONSTANS (CO) serves as the key regulator protein of the photoperiodic flowering times of Arabidopsis (''Arabidopsis thaliana''). CONSTANS (CO) is able to modulate flowering times through the regulation of the florigen hormone FT (FLOWERING LOCUS T). CO regulation is incredibly specific to the growth stage, season, and time of day. In the presence of light stimulus, CO increases the production of FT (FLOWERING LOCUS T) which then begins the process of flower differentiation. Signals from the environment such as temperature and light availability can inversely act as inhibitors for FT. In complete darkness, CO is completely degraded and flowering is halted. Different lighting periods can result in varying accumulations of CO, which can reduce or increase the speed of flowering depending on light cues. Regulation of CO mRNA is controlled by the circadian rhythm of arabidopsis, particularly in enhancement of long days (LD). The nuclear protein GIGANTEA (GI) interacts with FLAVIN BINDING, KELCH REPEAT, F-BOX PROTEIN 1 (FKF1) to begin the degradation process with the use of DOF transcription factors known as Cycling Dof Factors (CDFs). CDFs are then able to bind to the CO promoter region and inhibit its expression during the morning, thus inhibiting flowering times. Since flowering times are incredibly specific, post translational CO activity is critical as peak mRNA expression is not necessarily concurrent with the exact time of CO activity. CO stability varies depending on light conditions. In the presence of blue light, CO stability is high as blue light impacts the photoreceptors PHYTOCHROME B (phyB) and CRYPTOCHROME 2 (CRY2). In red light, CO stability was poor as PHYB activity restricts flowering from occurring. Another key regulator of CO stability is proteasome. When there is darkness present and during the morning hours, proteasome works to degrade CO and thus prevent flowering from occurring. In light periods CO is stable and able to then activate FT to induce flowering. <br />
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== Evolutionary Conservation ==<br />
The CO/FT regulatory module is a highly conserved pathway that is seen in all flowering plants. The flowering period for any given plant is incredibly important for reproductive success and survival, thus flowering period regulating genes are highly conserved. Green algae contain the most preserved characteristics in the plant kingdom and contain Constans-like genes (COLs). Mutated genes in ''Chlamydomonas'' revealed an encoded protein that shared likeness to COLS. This protein had a conserved zinc finger region and two N-terminal B-boxes. When comparing the presence of these proteins to the evolutionary age of compared plants, the presence of COL genes in green algae is consistent with the hypothesis that these genes appeared prior to or shortly after the photosynthetic endosymbiotic event. While not proven, it is suggested that COLs play some role in photoperiod regulation. For example, in'' Chlamydomonas'', the protein CrCO was identified. MRNA accumulation did not correlate with the photoperiod of'' Chlamydomonas'', however, there was a correlation observed between the peak of the short day period and CrCO mRNA, suggesting that there is some retained photoperiod influence. Overall, phylogenetic evidence suggests the COLs evolved from a singular b-box and CCT to two b-boxes with an extensive CCT region. In other plants, the CO-FT pathway serves in a variety of development regulation for plant propagation and extremity development. In potatoes, the CO-FT pathway is involved in tuberization. In other plants such as in Chlamydomonas, CrCO also helps to regulate growth and cellular stability. Flowering regulation through CO and its homolog COLS suggests a strong conservation of photoperiod pathways. <br />
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== Relevance ==<br />
Much is still unknown about the pathway of the FT hormone when it is activated by CO. As the CO-FT model is a highly conserved pathway, understanding how modifications to the CO protein could further enhance agricultural yield and commercial value. As climate change continues to threaten weather conditions and seasonal length, photoperiods may be altered. These alterations can significantly disrupt flowering periods which is why it is critical to understand the regulation pathway of Constans (CO). In the future, it may be necessary to genetically alter flowering periods to correlate to accommodate changing climates and seasonsonal length change to preserve ecological reproduction patterns. Rupturing the intricate ecological patterns can cause significant ramifications to the food chain and overall health of an ecosystem. <br />
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</StructureSection><br />
== References ==<br />
<references/><br />
1. Federico Valverde, CONSTANS and the evolutionary origin of photoperiodic timing of flowering, Journal of Experimental Botany, Volume 62, Issue 8, May 2011, Pages 2453–2463, https://doi.org/10.1093/jxb/erq449<br />
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2. Khanna, Rajnish et al. “The Arabidopsis B-box zinc finger family.” The Plant cell vol. 21,11 (2009): 3416-20. doi:10.1105/tpc.109.069088<br />
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3. Kim, S. Y., Yu, X., & Michaels, S. D. (2008). Regulation of CONSTANS and FLOWERING LOCUS T expression in response to changing light quality. Plant physiology, 148(1), 269–279. https://doi.org/10.1104/pp.108.122606<br />
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4. Liu, Y., Lin, G., Yin, C. et al. B-box transcription factor 28 regulates flowering by interacting with constans. Sci Rep 10, 17789 (2020). https://doi.org/10.1038/s41598-020-74445-7</div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3554158User:Jason Telford/Telford Sandbox 12022-04-28T22:01:28Z<p>Jason Telford: </p>
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<div>==Insert pdb after this==<br />
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<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
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This is a test page page<br />
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[[Green_Fluorescent_Protein]]GFP<br />
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This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene<scene name='46/464795/1enh_export/1'>Text To Be Displayed</scene> authoring tools<br />
save page.<br />
Another <scene name='46/464795/1enh_export/3'>1enh</scene> export scene.<br />
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This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
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and this is a repeat of that reference<ref name=allergen/><br />
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Markdown language starts here:<br />
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* this is bold<br />
_this is_ bold<br />
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each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
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<scene name='46/464795/1enh_export/1'>1enh test scene link</scene><br />
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<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
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<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
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<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
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<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
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We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
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This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
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A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene> scene<scene name='46/464795/Junk_scene/2'> v2</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/sandbox_7&diff=3547379User:Jason Telford/sandbox 72022-04-19T17:52:14Z<p>Jason Telford: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1enh' size='340' side='right' caption='engrailed homeodomain scene=''><br />
This is a default text for your page '''Jason Telford/sandbox 7'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
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== Function ==<br />
<i>This is the function</i><br />
== Disease ==<br />
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== Relevance ==<br />
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== Structural highlights ==<br />
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This is my first big <scene name='90/908144/1enhtest_1/1'>scene</scene>.<br />
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== Not the Function ==<br />
Everything else<br />
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<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/sandbox_7&diff=3547375User:Jason Telford/sandbox 72022-04-19T17:43:20Z<p>Jason Telford: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1enh' size='340' side='right' caption='engrailed homeodomain scene=''><br />
This is a default text for your page '''Jason Telford/sandbox 7'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
<i>This is the function</i><br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
== Not the Function ==<br />
Everything else<br />
<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/sandbox_7&diff=3547373User:Jason Telford/sandbox 72022-04-19T17:42:11Z<p>Jason Telford: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/sandbox 7'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
<i>This is the function</i><br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
== Not the Function ==<br />
Everything else<br />
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<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/sandbox_7&diff=3547372User:Jason Telford/sandbox 72022-04-19T17:39:34Z<p>Jason Telford: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/sandbox 7'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
<i>This is the function</i><br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/sandbox_7&diff=3536691User:Jason Telford/sandbox 72022-03-29T14:45:12Z<p>Jason Telford: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...</p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/sandbox 7'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
This is the function<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford&diff=3522488User:Jason Telford2022-03-01T18:36:07Z<p>Jason Telford: </p>
<hr />
<div>*[[User:Jason Telford/sandbox 7]]<br />
<br />
*Professor of Chemistry at Maryville University, St. Louis, MO, USA<br />
*1995, Ph.D. Biological Inorganic Chemistry, University of California, Berkeley<br />
*1996-98, NIH Postdoctoral Scholar, California Institute of Technology</div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3396819User:Jason Telford/Telford Sandbox 12021-05-11T18:53:41Z<p>Jason Telford: </p>
<hr />
<div>==Insert pdb after this==<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page page<br />
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This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene<scene name='46/464795/1enh_export/1'>Text To Be Displayed</scene> authoring tools<br />
save page.<br />
Another <scene name='46/464795/1enh_export/3'>1enh</scene> export scene.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
Markdown language starts here:<br />
<br />
* this is bold<br />
_this is_ bold<br />
<br />
<br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enh_export/1'>1enh test scene link</scene><br />
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<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
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<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
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<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
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<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
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We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
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This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
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A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene> scene<scene name='46/464795/Junk_scene/2'> v2</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=Sulfide_quinone_oxidoreductase&diff=3393928Sulfide quinone oxidoreductase2021-04-29T15:06:38Z<p>Jason Telford: </p>
<hr />
<div>==Introduction to SQOR==<br />
Oxidoreductases are used to catalyze the movement of electrons between an oxidant and a reductant. Sulfide quinone oxidoreductase, <scene name='88/881543/Sqor_-_1/1'>SQOR</scene>, is an integral membrane protein used in the mitochondria during metabolism to oxidize hydrogen sulfide with assistance from a quinone (Jackson et al., 2019). This enzyme marks the committed step of the sulfide oxidation pathway. SQOR is also the enzyme involved in the irreversible step of hydrogen sulfide metabolism (Landry et al., 2019). In the environment, sulfide is found in aquatic marine environments and in soil but is typically produced by prokaryotes and eukaryotes through catabolism (Lencina et al., 2013). SQOR uses coenzyme Q as the electron acceptor, and it uses sulfide, sulfite, cyanide, or glutathione as a sulfane acceptor (“SQOR - Sulfide:quinone oxidoreductase, mitochondrial precursor”, 2021). Sulfane, or thiosulfoxide sulfur, is an essential molecule in the regulation of cellular processes. It has the capabilities to create cofactors as well as modify enzymatic activities (Toohey & Cooper, 2014). Coenzyme Q is essential for electron transfer in metabolic processes, anabolic and catabolic. In bacterial SQOR, cytochrome C is used as the electron acceptor (Jackson et al., 2019). The gasotransmitter, hydrogen sulfide or H2S, acts in biological processes and can be used as a target in drug interactions, which can be observed in mitochondrial metabolism (Jackson et al., 2019). Hydrogen sulfide signaling is used in the cardiovascular system to prevent the development of cardiovascular diseases, such as hypertension (Jackson et al., 2019). SQOR can also be found in bacteria, producing sulfane sulfur metabolites (Jackson et al., 2019). In contrast to human SQOR, it does not use a sulfane acceptor. In humans, SQOR belongs to the flavoprotein disulfide reductase (FDR) family (Miller, 2013). SQOR is also in the pyridine nucleotide- disulfide oxidoreductase family. There are also various types of SQORs found, such as SqrA, SqrB, SqrC, SqrD, SqrE, and SqrF (Lencina, 2013). The crystallization method used on this SQOR was vapor diffusion at a pH of 7, which in result, gave indicators of the length and structure of this monumental enzyme. <br />
<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Structure of Human Sulfide Quinone Oxidoreductase'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structure ==<br />
In PDB, this structure is marked as 6OI5 and is noted as the crystal structure of human sulfide quinone oxidoreductase. This enzyme is made up of two different amino acid chains. It contains the ligand, flavin-adenine dinucleotide (FAD). The FAD is noncovalently connected to the main subunit, and it is in the oxidized state waiting to be reduced (Jackson et al., 2019). In this structure specifically, one residue was modified into s-mercaptocysteine. This modified residue is considered L-type linking and is a potential drug target (Bank, R. P. D., 2020). In humans, the SQOR is made of two tandem[http://https://proteopedia.org/wiki/index.php/Rossman_fold Rossman folds], and a C-terminal made up of two helices. Rossmann folds are composed of six beta sheets that are arranged parallel to one another with alpha helices connecting the first three strands (Jackson et al., 2019). The C-terminal extends outward from the main body of the enzyme, and is amphipathic, containing both hydrophobic and hydrophilic portions within the enzyme. The <scene name='88/881543/Hydrophobic_regions_-1/1'>hydrophobic region</scene> of the protruding C-terminal faces out from the membrane. Following that C-terminal, a penultimate helix arises and is very hydrophobic. It contains 16 hydrophobic residues, 11 of which are facing away from the membrane. The nonpolar residues on this penultimate helix are most tyrosines and methionines, and they face towards a cavity, indicating a binding location for coenzyme Q (Jackson et al., 2019). Due to the hydrophobic areas making contact to the inner areas of the membrane, the enzyme would be able to make its way towards coenzyme Q and pass off electrons to it. SQOR contains an indent that is electropositive, which will be the location for sulfane sulfur acceptors to bind. Within the middle of the indent, there is an opening just large enough to give access to the one of the reactive cysteine residues. There is a hydrogen sulfide oxidizing site which connects to a hydrophilic pocket, or tunnel, leading to the location where coenzyme Q will eventually bind (Jackson et al., 2019). Chain A is composed of alpha helices, beta sheets and has numerous binding sites. Chain A also contains many FAD-binding spots. A disulfide bridge connects the positions 161 to 339, or 201 to 379, also denoted by PDB, together (Bank, R. P. D., 2020). The spacing between the two cysteine active sites makes strong bridging between the two. The positions of the disulfide bonds are Cys201 and Cys379. Chain B is very much identical to Chain A in that it contains a <scene name='88/881543/Disulfide_bridge-1/6'>disulfide</scene> bridge at the positions Cys201 and Cys379 (Landry et al., 2019). Chain B is also made up of alpha helices and beta sheets. It is very much identical to Chain A in that it has a disulfide bridge at the same residues (Bank, 2020). The resolution of sulfide quinone oxidoreductase is 2.81 angstroms, and the sequence is 418 residues in length (Bank, R. P. D., 2020). The surface of SQOR that is facing the membrane is characterized by different charges and properties (Jackson et al., 2019). The surface that is facing towards the cellular matrix contains hydrophobic areas, as well as the hydrophobic coenzyme Q binding pocket. The <scene name='88/881543/Hydrophobic_regions_-1/3'>surface</scene> facing the cellular matrix also has a very large positive charge which interacts with the phospholipid bilayer, which is negative. The other side of SQOR contains a large negative surface, where one of the Rossmann folds is located and where the electropositive divet is located (Jackson et al., 2019). <br />
<br />
== Function ==<br />
Sulfide quinone oxidoreductase is essential in maintaining sulfide homeostasis, the synthesis of energy through the transfer of electrons, and detoxifying sulfide. Specific functions of SQOR include quinone binding and catalytic activity. Another activity involving SQOR is oxidoreductase functionality. Oxidoreductases can act as either an oxidase or a dehydrogenase (“What are Oxidoreductases?”, 2005). In this enzyme, as stated previously, there are FAD-binding sites, leading to the reduction of FAD+ to FADH2, and dehydrogenases will transfer a hydrogen ion to the accepting FAD+. Besides SQOR there are other examples of oxidoreductases within the body, and they are; peroxidases which are located within peroxisome, waste removing organelles, and hydroxylases, which will add a hydroxyl group to a molecule (“What are Oxidoreductases?”, 2005). Many cellular components are involved or affected by SQOR including; the cytoplasm and the mitochondrial inner and outer membranes. Oxidoreductases play significant roles in both anaerobic and aerobic metabolism. More specifically, this SQOR enzyme plays a role in mitochondrial metabolism. As previously stated, the main process of SQOR is to metabolize hydrogen sulfide, H2S, but SQOR can also metabolize H2S2 if no sulfane acceptor is present. This SQOR was exposed to a pH of 7, but it can also exist in a more alkaline pH of 8.5 and 7.5. Cyanide appears to be the acceptor when the pH is at 8.5. At the same time, sulfide is the primary acceptor when the pH is at 7. Overall, SQOR functions optimally at physiological pH (Jackson et al., 2012).<br />
== Hydrogen Sulfide Metabolism ==<br />
Hydrogen sulfide metabolism occurs within the mitochondria and consists of about four enzymes. Hydrogen sulfide is flammable, toxic, and has an unpleasant smell. It controls many physiological processes in the cardiovascular, gastrointestinal, and nervous system (Landry et al., 2019). The first enzyme involved in the catabolism of hydrogen sulfide is SQOR. The role of SQOR in hydrogen sulfide metabolism is to create thiosulfate by transferring sulfane sulfur atoms from the hydrogen sulfide present (Quinzii et al., 2017). Electrons are transported to the electron transport chain of the mitochondria to reduce coenzyme Q, which occurs in the coenzyme Q binding pocket of SQOR. This is considered a half reaction for both parts because the first part of the reaction is where there is the catabolism of the hydrogen sulfide. The step of this reaction would be the pass off of electrons to coenzyme (Landry et al., 2019). Sulfur dioxygenases is the next enzyme that is used to convert GSH persulfide to sulfite. The sulfite produced then gets oxidized by sulfite oxidase to become sulfate. An alternate route to produce thiosulfate would be thiosulfate sulfurtransferase converting sulfide to the desired thiosulfate by adding a persulfide to it (Quinzii et al., 2017). <br />
== Uses of SQOR ==<br />
Sulfide quinone oxidoreductase is essential for maintaining healthy levels of hydrogen sulfide within the body. This makes SQOR a drug target for pharmaceutical companies. As stated, SQOR can use a multitude of acceptors, also making it open for more diverse ideas in drug design. Hydrogen sulfide’s role within the cardiovascular system indicates SQOR is an important enzyme in increasing or lowering H2S levels. Heart failure has been recently seen to be linked to hydrogen sulfide. With that, pharmaceutical companies are seeing this as a possible point of interest in creating potential cardiovascular drugs. Additionally, hydrogen sulfide aids in post-translational modification (Jackson et al., 2019). Hydrogen sulfide also regulates ion channels and aids in neuron transmission (Quinzii et al., 2017). Due to its importance in maintaining physiological levels of hydrogen sulfide, SQOR is a possible drug target to decrease cardiovascular and neurological complications and aid in biological processes. Due to hydrogen sulfide being present in the gastrointestinal tract, it is being seen that there is a correlation between levels of hydrogen sulfide and Crohn's disease. It has been seen in Crohn’s patients that there is a substantial amount of hydrogen sulfide and lower amounts of the hydrogen sulfide metabolism enzymes (Quinzii et al., 2017). For this reason SQOR has another reason to become a drug target.<br />
<br />
== Landmarks on SQOR ==<br />
The FAD binding site on SQOR is a significant landmark in SQOR. FAD is <scene name='88/881543/Fad_-_1/1'>flavin adenine dinucleotide</scene> and is a product of condensation reaction between adenine diphosphate and riboflavin. There are about eleven FAD-binding locations on sulfide quinone oxidoreductase (Bank, R. P. D., 2020). FAD-binding involves twelve hydrogen bonds to the enzyme, with an addition of interactions with dipoles electrostatically (Jackson et al., 2019). It is important to note that Lys207 and Lys418 are located near FAD’s binding location, and they are both relatively basic residues. There are also two additional lysine residues at 200 and 344 that are located by the ribityl chain on the FAD (Jackson et al., 2019). Ribityl chains occur when a terminal hydroxyl group is removed. To help stabilize the charge of the flavin ring, the N-terminus on alpha helix 11 is positioned towards the FAD ring. In addition, alpha helix 1 helps neutralize the charge of the FAD (Jackson et al., 2019). On the surface of SQOR that is facing the membrane, there is an entrance which leads to the CoQ-binding pocket. Coenzyme Q is very prevalent within cell membranes. This lipid electron transporter, as previously mentioned, is important in SQOR’s pathway to metabolize hydrogen sulfide (Jackson et al., 2019). Decreased prevalence of coenzyme Q affects the oxidation of hydrogen sulfide, and can cause skin fibroblasts in humans, as recently studied (Quinzii et al., 2017). <br />
<br />
<br />
<br />
This is a sample <scene name='88/881543/Sqor_-_1/1'>scene</scene> created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=Sulfide_quinone_oxidoreductase&diff=3393927Sulfide quinone oxidoreductase2021-04-29T14:54:30Z<p>Jason Telford: </p>
<hr />
<div>==Introduction to SQOR==<br />
Oxidoreductases are used to catalyze the movement of electrons between an oxidant and a reductant. Sulfide quinone oxidoreductase, <scene name='88/881543/Sqor_-_1/1'>SQOR</scene>, is an integral membrane protein used in the mitochondria during metabolism to oxidize hydrogen sulfide with assistance from a quinone (Jackson et al., 2019). This enzyme marks the committed step of the sulfide oxidation pathway. SQOR is also the enzyme involved in the irreversible step of hydrogen sulfide metabolism (Landry et al., 2019). In the environment, sulfide is found in aquatic marine environments and in soil but is typically produced by prokaryotes and eukaryotes through catabolism (Lencina et al., 2013). SQOR uses coenzyme Q as the electron acceptor, and it uses sulfide, sulfite, cyanide, or glutathione as a sulfane acceptor (“SQOR - Sulfide:quinone oxidoreductase, mitochondrial precursor”, 2021). Sulfane, or thiosulfoxide sulfur, is an essential molecule in the regulation of cellular processes. It has the capabilities to create cofactors as well as modify enzymatic activities (Toohey & Cooper, 2014). Coenzyme Q is essential for electron transfer in metabolic processes, anabolic and catabolic. In bacterial SQOR, cytochrome C is used as the electron acceptor (Jackson et al., 2019). The gasotransmitter, hydrogen sulfide or H2S, acts in biological processes and can be used as a target in drug interactions, which can be observed in mitochondrial metabolism (Jackson et al., 2019). Hydrogen sulfide signaling is used in the cardiovascular system to prevent the development of cardiovascular diseases, such as hypertension (Jackson et al., 2019). SQOR can also be found in bacteria, producing sulfane sulfur metabolites (Jackson et al., 2019). In contrast to human SQOR, it does not use a sulfane acceptor. In humans, SQOR belongs to the flavoprotein disulfide reductase (FDR) family (Miller, 2013). SQOR is also in the pyridine nucleotide- disulfide oxidoreductase family. There are also various types of SQORs found, such as SqrA, SqrB, SqrC, SqrD, SqrE, and SqrF (Lencina, 2013). The crystallization method used on this SQOR was vapor diffusion at a pH of 7, which in result, gave indicators of the length and structure of this monumental enzyme. <br />
<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Structure of Human Sulfide Quinone Oxidoreductase'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structure ==<br />
In PDB, this structure is marked as 6OI5 and is noted as the crystal structure of human sulfide quinone oxidoreductase. This enzyme is made up of two different amino acid chains. It contains the ligand, flavin-adenine dinucleotide (FAD). The FAD is noncovalently connected to the main subunit, and it is in the oxidized state waiting to be reduced (Jackson et al., 2019). In this structure specifically, one residue was modified into s-mercaptocysteine. This modified residue is considered L-type linking and is a potential drug target (Bank, R. P. D., 2020). In humans, the SQOR is made of two tandem[http://https://proteopedia.org/wiki/index.php/Rossman_fold Rossman folds], and a C-terminal made up of two helices. Rossmann folds are composed of six beta sheets that are arranged parallel to one another with alpha helices connecting the first three strands (Jackson et al., 2019). The C-terminal extends outward from the main body of the enzyme, and is amphipathic, containing both hydrophobic and hydrophilic portions within the enzyme. The <scene name='88/881543/Hydrophobic_regions_-1/1'>hydrophobic region</scene> of the protruding C-terminal faces out from the membrane. Following that C-terminal, a penultimate helix arises and is very hydrophobic. It contains 16 hydrophobic residues, 11 of which are facing away from the membrane. The nonpolar residues on this penultimate helix are most tyrosines and methionines, and they face towards a cavity, indicating a binding location for coenzyme Q (Jackson et al., 2019). Due to the hydrophobic areas making contact to the inner areas of the membrane, the enzyme would be able to make its way towards coenzyme Q and pass off electrons to it. SQOR contains an indent that is electropositive, which will be the location for sulfane sulfur acceptors to bind. Within the middle of the indent, there is an opening just large enough to give access to the one of the reactive cysteine residues. There is a hydrogen sulfide oxidizing site which connects to a hydrophilic pocket, or tunnel, leading to the location where coenzyme Q will eventually bind (Jackson et al., 2019). Chain A is composed of alpha helices, beta sheets and has numerous binding sites. Chain A also contains many FAD-binding spots. A disulfide bridge connects the positions 161 to 339, or 201 to 379, also denoted by PDB, together (Bank, R. P. D., 2020). The spacing between the two cysteine active sites makes strong bridging between the two. The positions of the disulfide bonds are Cys201 and Cys379. Chain B is very much identical to Chain A in that it contains a <scene name='88/881543/Disulfide_bridge-1/4'>disulfide</scene> bridge at the positions Cys201 and Cys379 (Landry et al., 2019). Chain B is also made up of alpha helices and beta sheets. It is very much identical to Chain A in that it has a disulfide bridge at the same residues (Bank, 2020). The resolution of sulfide quinone oxidoreductase is 2.81 angstroms, and the sequence is 418 residues in length (Bank, R. P. D., 2020). The surface of SQOR that is facing the membrane is characterized by different charges and properties (Jackson et al., 2019). The surface that is facing towards the cellular matrix contains hydrophobic areas, as well as the hydrophobic coenzyme Q binding pocket. The <scene name='88/881543/Hydrophobic_regions_-1/3'>surface</scene> facing the cellular matrix also has a very large positive charge which interacts with the phospholipid bilayer, which is negative. The other side of SQOR contains a large negative surface, where one of the Rossmann folds is located and where the electropositive divet is located (Jackson et al., 2019). <br />
<br />
== Function ==<br />
Sulfide quinone oxidoreductase is essential in maintaining sulfide homeostasis, the synthesis of energy through the transfer of electrons, and detoxifying sulfide. Specific functions of SQOR include quinone binding and catalytic activity. Another activity involving SQOR is oxidoreductase functionality. Oxidoreductases can act as either an oxidase or a dehydrogenase (“What are Oxidoreductases?”, 2005). In this enzyme, as stated previously, there are FAD-binding sites, leading to the reduction of FAD+ to FADH2, and dehydrogenases will transfer a hydrogen ion to the accepting FAD+. Besides SQOR there are other examples of oxidoreductases within the body, and they are; peroxidases which are located within peroxisome, waste removing organelles, and hydroxylases, which will add a hydroxyl group to a molecule (“What are Oxidoreductases?”, 2005). Many cellular components are involved or affected by SQOR including; the cytoplasm and the mitochondrial inner and outer membranes. Oxidoreductases play significant roles in both anaerobic and aerobic metabolism. More specifically, this SQOR enzyme plays a role in mitochondrial metabolism. As previously stated, the main process of SQOR is to metabolize hydrogen sulfide, H2S, but SQOR can also metabolize H2S2 if no sulfane acceptor is present. This SQOR was exposed to a pH of 7, but it can also exist in a more alkaline pH of 8.5 and 7.5. Cyanide appears to be the acceptor when the pH is at 8.5. At the same time, sulfide is the primary acceptor when the pH is at 7. Overall, SQOR functions optimally at physiological pH (Jackson et al., 2012).<br />
== Hydrogen Sulfide Metabolism ==<br />
Hydrogen sulfide metabolism occurs within the mitochondria and consists of about four enzymes. Hydrogen sulfide is flammable, toxic, and has an unpleasant smell. It controls many physiological processes in the cardiovascular, gastrointestinal, and nervous system (Landry et al., 2019). The first enzyme involved in the catabolism of hydrogen sulfide is SQOR. The role of SQOR in hydrogen sulfide metabolism is to create thiosulfate by transferring sulfane sulfur atoms from the hydrogen sulfide present (Quinzii et al., 2017). Electrons are transported to the electron transport chain of the mitochondria to reduce coenzyme Q, which occurs in the coenzyme Q binding pocket of SQOR. This is considered a half reaction for both parts because the first part of the reaction is where there is the catabolism of the hydrogen sulfide. The step of this reaction would be the pass off of electrons to coenzyme (Landry et al., 2019). Sulfur dioxygenases is the next enzyme that is used to convert GSH persulfide to sulfite. The sulfite produced then gets oxidized by sulfite oxidase to become sulfate. An alternate route to produce thiosulfate would be thiosulfate sulfurtransferase converting sulfide to the desired thiosulfate by adding a persulfide to it (Quinzii et al., 2017). <br />
== Uses of SQOR ==<br />
Sulfide quinone oxidoreductase is essential for maintaining healthy levels of hydrogen sulfide within the body. This makes SQOR a drug target for pharmaceutical companies. As stated, SQOR can use a multitude of acceptors, also making it open for more diverse ideas in drug design. Hydrogen sulfide’s role within the cardiovascular system indicates SQOR is an important enzyme in increasing or lowering H2S levels. Heart failure has been recently seen to be linked to hydrogen sulfide. With that, pharmaceutical companies are seeing this as a possible point of interest in creating potential cardiovascular drugs. Additionally, hydrogen sulfide aids in post-translational modification (Jackson et al., 2019). Hydrogen sulfide also regulates ion channels and aids in neuron transmission (Quinzii et al., 2017). Due to its importance in maintaining physiological levels of hydrogen sulfide, SQOR is a possible drug target to decrease cardiovascular and neurological complications and aid in biological processes. Due to hydrogen sulfide being present in the gastrointestinal tract, it is being seen that there is a correlation between levels of hydrogen sulfide and Crohn's disease. It has been seen in Crohn’s patients that there is a substantial amount of hydrogen sulfide and lower amounts of the hydrogen sulfide metabolism enzymes (Quinzii et al., 2017). For this reason SQOR has another reason to become a drug target.<br />
<br />
== Landmarks on SQOR ==<br />
The FAD binding site on SQOR is a significant landmark in SQOR. FAD is <scene name='88/881543/Fad_-_1/1'>flavin adenine dinucleotide</scene> and is a product of condensation reaction between adenine diphosphate and riboflavin. There are about eleven FAD-binding locations on sulfide quinone oxidoreductase (Bank, R. P. D., 2020). FAD-binding involves twelve hydrogen bonds to the enzyme, with an addition of interactions with dipoles electrostatically (Jackson et al., 2019). It is important to note that Lys207 and Lys418 are located near FAD’s binding location, and they are both relatively basic residues. There are also two additional lysine residues at 200 and 344 that are located by the ribityl chain on the FAD (Jackson et al., 2019). Ribityl chains occur when a terminal hydroxyl group is removed. To help stabilize the charge of the flavin ring, the N-terminus on alpha helix 11 is positioned towards the FAD ring. In addition, alpha helix 1 helps neutralize the charge of the FAD (Jackson et al., 2019). On the surface of SQOR that is facing the membrane, there is an entrance which leads to the CoQ-binding pocket. Coenzyme Q is very prevalent within cell membranes. This lipid electron transporter, as previously mentioned, is important in SQOR’s pathway to metabolize hydrogen sulfide (Jackson et al., 2019). Decreased prevalence of coenzyme Q affects the oxidation of hydrogen sulfide, and can cause skin fibroblasts in humans, as recently studied (Quinzii et al., 2017). <br />
<br />
<br />
<br />
This is a sample <scene name='88/881543/Sqor_-_1/1'>scene</scene> created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=Sulfide_quinone_oxidoreductase&diff=3393924Sulfide quinone oxidoreductase2021-04-29T14:43:44Z<p>Jason Telford: </p>
<hr />
<div>==Introduction to SQOR==<br />
Oxidoreductases are used to catalyze the movement of electrons between an oxidant and a reductant. Sulfide quinone oxidoreductase, <scene name='88/881543/Sqor_-_1/1'>SQOR</scene>, is an integral membrane protein used in the mitochondria during metabolism to oxidize hydrogen sulfide with assistance from a quinone (Jackson et al., 2019). This enzyme marks the committed step of the sulfide oxidation pathway. SQOR is also the enzyme involved in the irreversible step of hydrogen sulfide metabolism (Landry et al., 2019). In the environment, sulfide is found in aquatic marine environments and in soil but is typically produced by prokaryotes and eukaryotes through catabolism (Lencina et al., 2013). SQOR uses coenzyme Q as the electron acceptor, and it uses sulfide, sulfite, cyanide, or glutathione as a sulfane acceptor (“SQOR - Sulfide:quinone oxidoreductase, mitochondrial precursor”, 2021). Sulfane, or thiosulfoxide sulfur, is an essential molecule in the regulation of cellular processes. It has the capabilities to create cofactors as well as modify enzymatic activities (Toohey & Cooper, 2014). Coenzyme Q is essential for electron transfer in metabolic processes, anabolic and catabolic. In bacterial SQOR, cytochrome C is used as the electron acceptor (Jackson et al., 2019). The gasotransmitter, hydrogen sulfide or H2S, acts in biological processes and can be used as a target in drug interactions, which can be observed in mitochondrial metabolism (Jackson et al., 2019). Hydrogen sulfide signaling is used in the cardiovascular system to prevent the development of cardiovascular diseases, such as hypertension (Jackson et al., 2019). SQOR can also be found in bacteria, producing sulfane sulfur metabolites (Jackson et al., 2019). In contrast to human SQOR, it does not use a sulfane acceptor. In humans, SQOR belongs to the flavoprotein disulfide reductase (FDR) family (Miller, 2013). SQOR is also in the pyridine nucleotide- disulfide oxidoreductase family. There are also various types of SQORs found, such as SqrA, SqrB, SqrC, SqrD, SqrE, and SqrF (Lencina, 2013). The crystallization method used on this SQOR was vapor diffusion at a pH of 7, which in result, gave indicators of the length and structure of this monumental enzyme. <br />
<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Structure of Human Sulfide Quinone Oxidoreductase'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structure ==<br />
In PDB, this structure is marked as 6OI5 and is noted as the crystal structure of human sulfide quinone oxidoreductase. This enzyme is made up of two different amino acid chains. It contains the ligand, flavin-adenine dinucleotide (FAD). The FAD is noncovalently connected to the main subunit, and it is in the oxidized state waiting to be reduced (Jackson et al., 2019). In this structure specifically, one residue was modified into s-mercaptocysteine. This modified residue is considered L-type linking and is a potential drug target (Bank, R. P. D., 2020). In humans, the SQOR is made of two tandem[http://https://proteopedia.org/wiki/index.php/Rossman_fold Rossman folds], and a C-terminal made up of two helices. Rossmann folds are composed of six beta sheets that are arranged parallel to one another with alpha helices connecting the first three strands (Jackson et al., 2019). The C-terminal extends outward from the main body of the enzyme, and is amphipathic, containing both hydrophobic and hydrophilic portions within the enzyme. The <scene name='88/881543/Hydrophobic_regions_-1/1'>hydrophobic region</scene> of the protruding C-terminal faces out from the membrane. Following that C-terminal, a penultimate helix arises and is very hydrophobic. It contains 16 hydrophobic residues, 11 of which are facing away from the membrane. The nonpolar residues on this penultimate helix are most tyrosines and methionines, and they face towards a cavity, indicating a binding location for coenzyme Q (Jackson et al., 2019). Due to the hydrophobic areas making contact to the inner areas of the membrane, the enzyme would be able to make its way towards coenzyme Q and pass off electrons to it. SQOR contains an indent that is electropositive, which will be the location for sulfane sulfur acceptors to bind. Within the middle of the indent, there is an opening just large enough to give access to the one of the reactive cysteine residues. There is a hydrogen sulfide oxidizing site which connects to a hydrophilic pocket, or tunnel, leading to the location where coenzyme Q will eventually bind (Jackson et al., 2019). Chain A is composed of alpha helices, beta sheets and has numerous binding sites. Chain A also contains many FAD-binding spots. A disulfide bridge connects the positions 161 to 339, or 201 to 379, also denoted by PDB, together (Bank, R. P. D., 2020). The spacing between the two cysteine active sites makes strong bridging between the two. The positions of the disulfide bonds are Cys201 and Cys379. Chain B is very much identical to Chain A in that it contains a <scene name='88/881543/Disulfide_bridge-1/4'>disulfide</scene> bridge at the positions Cys201 and Cys379 (Landry et al., 2019). Chain B is also made up of alpha helices and beta sheets. It is very much identical to Chain A in that it has a disulfide bridge at the same residues (Bank, 2020). The resolution of sulfide quinone oxidoreductase is 2.81 angstroms, and the sequence is 418 residues in length (Bank, R. P. D., 2020). The surface of SQOR that is facing the membrane is characterized by different charges and properties (Jackson et al., 2019). The surface that is facing towards the cellular matrix contains hydrophobic areas, as well as the hydrophobic coenzyme Q binding pocket. The surface facing the cellular matrix also has a very large positive charge which interacts with the phospholipid bilayer, which is negative. The other side of SQOR contains a large negative surface, where one of the Rossmann folds is located and where the electropositive divet is located (Jackson et al., 2019). <br />
<br />
== Function ==<br />
Sulfide quinone oxidoreductase is essential in maintaining sulfide homeostasis, the synthesis of energy through the transfer of electrons, and detoxifying sulfide. Specific functions of SQOR include quinone binding and catalytic activity. Another activity involving SQOR is oxidoreductase functionality. Oxidoreductases can act as either an oxidase or a dehydrogenase (“What are Oxidoreductases?”, 2005). In this enzyme, as stated previously, there are FAD-binding sites, leading to the reduction of FAD+ to FADH2, and dehydrogenases will transfer a hydrogen ion to the accepting FAD+. Besides SQOR there are other examples of oxidoreductases within the body, and they are; peroxidases which are located within peroxisome, waste removing organelles, and hydroxylases, which will add a hydroxyl group to a molecule (“What are Oxidoreductases?”, 2005). Many cellular components are involved or affected by SQOR including; the cytoplasm and the mitochondrial inner and outer membranes. Oxidoreductases play significant roles in both anaerobic and aerobic metabolism. More specifically, this SQOR enzyme plays a role in mitochondrial metabolism. As previously stated, the main process of SQOR is to metabolize hydrogen sulfide, H2S, but SQOR can also metabolize H2S2 if no sulfane acceptor is present. This SQOR was exposed to a pH of 7, but it can also exist in a more alkaline pH of 8.5 and 7.5. Cyanide appears to be the acceptor when the pH is at 8.5. At the same time, sulfide is the primary acceptor when the pH is at 7. Overall, SQOR functions optimally at physiological pH (Jackson et al., 2012).<br />
== Hydrogen Sulfide Metabolism ==<br />
Hydrogen sulfide metabolism occurs within the mitochondria and consists of about four enzymes. Hydrogen sulfide is flammable, toxic, and has an unpleasant smell. It controls many physiological processes in the cardiovascular, gastrointestinal, and nervous system (Landry et al., 2019). The first enzyme involved in the catabolism of hydrogen sulfide is SQOR. The role of SQOR in hydrogen sulfide metabolism is to create thiosulfate by transferring sulfane sulfur atoms from the hydrogen sulfide present (Quinzii et al., 2017). Electrons are transported to the electron transport chain of the mitochondria to reduce coenzyme Q, which occurs in the coenzyme Q binding pocket of SQOR. This is considered a half reaction for both parts because the first part of the reaction is where there is the catabolism of the hydrogen sulfide. The step of this reaction would be the pass off of electrons to coenzyme (Landry et al., 2019). Sulfur dioxygenases is the next enzyme that is used to convert GSH persulfide to sulfite. The sulfite produced then gets oxidized by sulfite oxidase to become sulfate. An alternate route to produce thiosulfate would be thiosulfate sulfurtransferase converting sulfide to the desired thiosulfate by adding a persulfide to it (Quinzii et al., 2017). <br />
== Uses of SQOR ==<br />
Sulfide quinone oxidoreductase is essential for maintaining healthy levels of hydrogen sulfide within the body. This makes SQOR a drug target for pharmaceutical companies. As stated, SQOR can use a multitude of acceptors, also making it open for more diverse ideas in drug design. Hydrogen sulfide’s role within the cardiovascular system indicates SQOR is an important enzyme in increasing or lowering H2S levels. Heart failure has been recently seen to be linked to hydrogen sulfide. With that, pharmaceutical companies are seeing this as a possible point of interest in creating potential cardiovascular drugs. Additionally, hydrogen sulfide aids in post-translational modification (Jackson et al., 2019). Hydrogen sulfide also regulates ion channels and aids in neuron transmission (Quinzii et al., 2017). Due to its importance in maintaining physiological levels of hydrogen sulfide, SQOR is a possible drug target to decrease cardiovascular and neurological complications and aid in biological processes. Due to hydrogen sulfide being present in the gastrointestinal tract, it is being seen that there is a correlation between levels of hydrogen sulfide and Crohn's disease. It has been seen in Crohn’s patients that there is a substantial amount of hydrogen sulfide and lower amounts of the hydrogen sulfide metabolism enzymes (Quinzii et al., 2017). For this reason SQOR has another reason to become a drug target.<br />
<br />
== Landmarks on SQOR ==<br />
The FAD binding site on SQOR is a significant landmark in SQOR. FAD is <scene name='88/881543/Fad_-_1/1'>flavin adenine dinucleotide</scene> and is a product of condensation reaction between adenine diphosphate and riboflavin. There are about eleven FAD-binding locations on sulfide quinone oxidoreductase (Bank, R. P. D., 2020). FAD-binding involves twelve hydrogen bonds to the enzyme, with an addition of interactions with dipoles electrostatically (Jackson et al., 2019). It is important to note that Lys207 and Lys418 are located near FAD’s binding location, and they are both relatively basic residues. There are also two additional lysine residues at 200 and 344 that are located by the ribityl chain on the FAD (Jackson et al., 2019). Ribityl chains occur when a terminal hydroxyl group is removed. To help stabilize the charge of the flavin ring, the N-terminus on alpha helix 11 is positioned towards the FAD ring. In addition, alpha helix 1 helps neutralize the charge of the FAD (Jackson et al., 2019). On the surface of SQOR that is facing the membrane, there is an entrance which leads to the CoQ-binding pocket. Coenzyme Q is very prevalent within cell membranes. This lipid electron transporter, as previously mentioned, is important in SQOR’s pathway to metabolize hydrogen sulfide (Jackson et al., 2019). Decreased prevalence of coenzyme Q affects the oxidation of hydrogen sulfide, and can cause skin fibroblasts in humans, as recently studied (Quinzii et al., 2017). <br />
<br />
<br />
<br />
This is a sample <scene name='88/881543/Sqor_-_1/1'>scene</scene> created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3393813User:Jason Telford/Telford Sandbox 22021-04-28T19:25:25Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1pob' size='500' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
Cobra Venom Scene1 -click <scene name='87/875653/Cobravenom1/1'>here</scene>.<br />
<br />
Cobra Venom Scene2- click <scene name='87/875653/Cobravenom2/1'>here</scene><br />
<br />
Cobra Venom Scene3- click <scene name='87/875653/Cobravenom3/1'>here</scene><br />
<br />
Phospholipase A2 in complex with <scene name='87/875653/1mlm1/1'>myristic acid</scene><br />
<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3393812User:Jason Telford/Telford Sandbox 12021-04-28T19:22:39Z<p>Jason Telford: </p>
<hr />
<div>==Insert pdb after this==<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene<scene name='46/464795/1enh_export/1'>Text To Be Displayed</scene> authoring tools<br />
save page.<br />
Another <scene name='46/464795/1enh_export/3'>1enh</scene> export scene.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enh_export/1'>1enh test scene link</scene><br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene> scene<scene name='46/464795/Junk_scene/2'> v2</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3393811User:Jason Telford/Telford Sandbox 12021-04-28T19:21:57Z<p>Jason Telford: </p>
<hr />
<div>==Insert pdb after this==<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene<scene name='46/464795/1enh_export/1'>Text To Be Displayed</scene> authoring tools<br />
save page.<br />
Another <scene name='46/464795/1enh_export/3'>1enh</scene> export scene.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enh_export/1'>1enh test scene link</scene><br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene> scene<scene name='46/464795/Junk_scene/2'> v2</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Sandbox_3&diff=3374519User:Jason Telford/Sandbox 32021-03-28T17:13:17Z<p>Jason Telford: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Sandbox 3'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
C<br />
== Disease ==<br />
D<br />
== Irrelevance ==<br />
E<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Sandbox_3&diff=3374518User:Jason Telford/Sandbox 32021-03-28T17:12:16Z<p>Jason Telford: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...</p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Sandbox 3'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
A<br />
== Disease ==<br />
B<br />
== Irrelevance ==<br />
C<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3371582User:Jason Telford/Telford Sandbox 22021-03-18T14:27:05Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1pob' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
Cobra Venom Scene1 -click <scene name='87/875653/Cobravenom1/1'>here</scene>.<br />
<br />
Cobra Venom Scene2- click <scene name='87/875653/Cobravenom2/1'>here</scene><br />
<br />
Cobra Venom Scene3- click <scene name='87/875653/Cobravenom3/1'>here</scene><br />
<br />
Phospholipase A2 in complex with <scene name='87/875653/1mlm1/1'>myristic acid</scene><br />
<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3371581User:Jason Telford/Telford Sandbox 22021-03-18T14:13:34Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1pob' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
Cobra Venom Scene1 -click <scene name='87/875653/Cobravenom1/1'>here</scene>.<br />
<br />
Cobra Venom Scene2- click <scene name='87/875653/Cobravenom2/1'>here</scene><br />
<br />
Cobra Venom Scene3- click <scene name='87/875653/Cobravenom3/1'>here</scene><br />
<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3371580User:Jason Telford/Telford Sandbox 22021-03-18T14:10:25Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1pob' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
Cobra Venom Scene1 -click <scene name='87/875653/Cobravenom1/1'>here</scene>.<br />
<br />
Cobra Venom Scene2- click <scene name='87/875653/Cobravenom2/1'>here</scene><br />
<br />
<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3371579User:Jason Telford/Telford Sandbox 22021-03-18T14:09:52Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1pob' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
Cobra Venom Scene1 -click <scene name='87/875653/Cobravenom1/1'>here</scene>.<scene name='87/875653/Cobravenom1/1'>1POB, includes ligand</scene><br />
<br />
Cobra Venom Scene2- click <scene name='87/875653/Cobravenom2/1'>here</scene><br />
<br />
<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3371578User:Jason Telford/Telford Sandbox 22021-03-18T14:08:13Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1pob' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
Cobra Venom Scene1 -click <scene name='87/875653/Cobravenom1/1'>here</scene>.<scene name='87/875653/Cobravenom1/1'>1POB, includes ligand</scene><br />
Cobra Venom Scene2- click <scene name='87/875653/Cobravenom2/1'>here</scene><br />
This is my inserted scene. Click <scene name='87/875653/Jrt_sandbox2_scene1/1'>here</scene>.<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3358144User:Jason Telford/Telford Sandbox 22021-02-18T19:05:50Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1enh' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
This is my inserted scene. Click <scene name='87/875653/Jrt_sandbox2_scene1/1'>here</scene>.<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3358143User:Jason Telford/Telford Sandbox 22021-02-18T18:51:58Z<p>Jason Telford: </p>
<hr />
<div>==My NEW heading (maybe something like 'Structure')==<br />
<StructureSection load='1enh' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== New Section ==<br />
Now we are going to change the text<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_2&diff=3358139User:Jason Telford/Telford Sandbox 22021-02-18T15:53:04Z<p>Jason Telford: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...</p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Jason Telford/Telford Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
this is new text<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford&diff=3340806User:Jason Telford2021-01-06T15:00:44Z<p>Jason Telford: </p>
<hr />
<div>*[[User:Jason Telford]]<br />
<br />
*Professor of Chemistry at Maryville University, St. Louis, MO, USA<br />
*1995, Ph.D. Biological Inorganic Chemistry, University of California, Berkeley<br />
*1996-98, NIH Postdoctoral Scholar, California Institute of Technology</div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford&diff=3340805User:Jason Telford2021-01-06T14:54:09Z<p>Jason Telford: </p>
<hr />
<div>*[[User:Jason Telford/Telford_Sandbox 2]]<br />
<br />
*Professor of Chemistry at Maryville University, St. Louis, MO, USA<br />
*1995, Ph.D. Biological Inorganic Chemistry, University of California, Berkeley<br />
*1996-98, NIH Postdoctoral Scholar, California Institute of Technology</div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3194226User:Jason Telford/Telford Sandbox 12020-04-15T17:59:05Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene<scene name='46/464795/1enh_export/1'>Text To Be Displayed</scene> authoring tools<br />
save page.<br />
Another <scene name='46/464795/1enh_export/3'>1enh</scene> export scene.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enh_export/1'>1enh test scene link</scene><br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene> scene<scene name='46/464795/Junk_scene/2'> v2</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3190883User:Jason Telford/Telford Sandbox 12020-04-13T17:52:08Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene<scene name='46/464795/1enh_export/1'>Text To Be Displayed</scene> authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enh_export/1'>1enh test scene link</scene><br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene> scene<scene name='46/464795/Junk_scene/2'> v2</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3166090User:Jason Telford/Telford Sandbox 12020-03-04T19:07:07Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene> scene<scene name='46/464795/Junk_scene/2'> v2</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3166085User:Jason Telford/Telford Sandbox 12020-03-04T18:55:38Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show <scene name='46/464795/Junk_scene/1'>scene</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3166074User:Jason Telford/Telford Sandbox 12020-03-04T17:50:58Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<ref name="my second reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3166073User:Jason Telford/Telford Sandbox 12020-03-04T17:50:00Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<br />
<br />
<ref name="my first reference"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref><br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3088176User:Jason Telford/Telford Sandbox 12019-09-09T18:03:27Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each <scene name='46/464795/1enh_export/1'>new</scene> scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=Nerve_agents_and_acetylcholinesterase&diff=3034544Nerve agents and acetylcholinesterase2019-04-29T15:48:49Z<p>Jason Telford: </p>
<hr />
<div>=='''Nerve Agents and Acetylcholinesterase'''==<br />
<StructureSection load='1eea' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
== '''Background''' ==<br />
In the current world, there are threats of war and new weapons all the time, it has become a constant in our society. Not all of these weapons are ones that the public would be able to tell were there until it was too late. These particular weapons are nerve agents, a particularly nasty bunch of chemicals that attack the human body and in most cases, cause death. The nerve agent that has gotten the most attention recently due to attacks within the last year is Novichok. Despite the name Novichok implying that it is a single chemical nerve agent, it is in fact a group of related molecules designed to kill. <ref name="Atch">Atchison, W. (2018, September 13). What is Novichok? A neurotoxicologist explains. Retrieved from http://theconversation.com/what-is-novichok-a-neurotoxicologist-explains-99736</ref> There are many different types of [[Media:Nerve agents.png|nerve agents,]] the most common being Novichok, <scene name='81/814054/Sarin_inhibiting_acetylcholine/2'>sarin</scene>, tabun, and <scene name='81/814054/Vx/2'>VX</scene>. Most of these agents were created accidently when researching pesticides and were found to be too toxic to use in agriculture and were therefore passed on to the military in whichever country the chemical was synthesized in. <ref name="cotton">Cotton, S. (2018). Nerve Agents: What Are They and How Do They Work? American Scientist, 106(3), may/june 2018, 138. doi:10.1511/2018.106.3.138</ref> Novichok for example was created somewhere between the 1970s and 1997. <ref name="May">May, P. (2018, August). Novichok. Retrieved from http://www.chm.bris.ac.uk/motm/novichok/novichokh.htm</ref><br />
In 1997, 193 countries signed the Chemical Weapons Convention treaty which banned development, production, and stockpiling of chemical weapons and required that these countries safely dispose of their reported chemical agents. This resulted in more than 67,000 tons of these chemicals being destroyed. <ref name="Gardiner"> Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88.</ref> This is due to the fact that nerve agents are so deadly and world leaders were afraid of a war using only these chemicals. <br />
<br />
== '''Importance''' ==<br />
Despite the Chemical Weapons Convention treaty, chemical warfare continues to be a threat to countries all over the world. Assassins use nerve agents as they are hard to track back to the person who created it, however it is not impossible to trace due to the residues that are left behind. People who wish to harm members of society do not need to give any warning when they attack using nerve agents and until the symptoms start to appear, it may not be known that an attack has even occurred. This can give a person time to get away from the area and not get caught, so being able to track the precursors is essential from a criminal justice perspective. <br />
Chemical warfare agents are classified as organophosphorus-based molecules due to them containing both phosphorus and carbon atoms at their core. <ref name="Klos">Kloske, M., & Witkiewicz, Z. (2019). Novichoks – The A group of organophosphorus chemical warfare agents. Chemosphere, 221, 673. doi:10.1016/j.chemosphere.2019.01.054</ref> These chemicals are called warfare agents due to their ability to disrupt the central nervous system communications and cause death to anyone exposed and are commonly used as acts of aggression. The reason these agents are so terrifying is due to the fact that they are colorless, odorless, have no taste, and can be introduced through any respiratory or gastrointestinal tract. <ref name="Gardiner">Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88</ref> The skin is also able to absorb nerve agents and it is extremely difficult to treat a person who has been exposed to one. Very small amounts of novichok are needed in order for it to be lethal, which adds to its already terrifying nature. <br />
Nerve agents are also dangerous because it is unknown how long they stay active once they are released. <ref name="Atch">Atchison, W. (2018, September 13). What is Novichok? A neurotoxicologist explains. Retrieved from http://theconversation.com/what-is-novichok-a-neurotoxicologist-explains-99736</ref> This presents a problem to first responders when an incident occurs. This was the case in England in 2018 when Novichok was used on Sergei Skripal and his daughter. The first responder was exposed to the nerve agent and had to undergo treatment in order to save his life. Novichok in particular is more dangerous than sarin or VX as it is 6-10 times stronger and therefore a smaller dose is required to produce the desired effect. <ref name="Atch">Atchison, W. (2018, September 13). What is Novichok? A neurotoxicologist explains. Retrieved from http://theconversation.com/what-is-novichok-a-neurotoxicologist-explains-99736</ref><br />
<br />
<br />
== '''What is Acetylcholine and its Enzyme''' ==<br />
<scene name='81/814054/Entire_molecule/6'>Acetylcholinesterase</scene> is one of the most efficient human enzymes that is known. It can hydrolyze around 600,000 <scene name='81/814054/Acetylcholinesterase_acetylcho/2'>acetylcholine</scene> molecules each minute which shows how essential it is to human life. <ref name="Stone"> Stone, R. (2018, September 25). How to defeat a nerve agent. Retrieved from https://www.sciencemag.org/news/2018/01/how-defeat-nerve-agent. </ref> Acetylcholinesterase has 3 active sites, according to current research, but nerve agents attack the primary site. The gorge that is located on the molecule near the <scene name='81/814054/Active_site_redone/4'>active site</scene> plays an essential role in the function of acetylcholine. <ref name="Xu">Xu, Y., Cheng, S., Sussman, J., Silman, I., & Jiang, H. (2017). Computational Studies on Acetylcholinesterases. Molecules, 22(8), 1324. doi:10.3390/molecules22081324</ref> The gorge allows the active site to open and close in order to control the flow of substrates that come to acetylcholine. Acetylcholinesterase was found to have 14 <scene name='81/814054/Aromatic_aa/1'>aromatic amino acids</scene> located around the opening to the gorge and this plays a role in the dipole moment within the molecule and it leads to a more symmetric charge distribution within the molecule. In 2017, it was found that acetylcholinesterase was a very effective catalyst and when a substrate interacts with an enzyme, that becomes the rate-limiting step. <ref name="Xu">Xu, Y., Cheng, S., Sussman, J., Silman, I., & Jiang, H. (2017). Computational Studies on Acetylcholinesterases. Molecules, 22(8), 1324. doi:10.3390/molecules22081324</ref><br />
<br />
== '''Parts of Nerve Agents''' ==<br />
Chemists have found that nerve agents that are derived from methylphosphonic dichloride [[Media:MPDC.gif|(DC)]] and use hydrogen fluoride (HF) to fluorinate the molecule, a residue of phosphorus hexafluoride (PF6) was always found. This residue was not found when any other fluorinators were used in the synthesis. This can help identify the starting chemicals that were used to create the nerve agents. <ref name="Gardiner">Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88</ref><br />
Despite the structure of these nerve agents remaining unknown, researchers have found that the various side chains that are added, which leads to the differences in naming, can affect the potency and how long the agent will last. <ref name="May">May, P. (2018, August). Novichok. Retrieved from http://www.chm.bris.ac.uk/motm/novichok/novichokh.htm</ref><br />
<br />
== '''Synthesis''' ==<br />
A Novichok is formed by combining two precursors to form a cyclic oxime ester. In this new molecule, the phosphorus atom is contained in a five-membered ring. When heated above zero, the ring that contains chlorine becomes destabilized and opens, allowing the Novichok to be formed. The process has a 30-60% efficiency. There are around 50 chemicals that are considered precursors and these are chemicals that are toxic and are not stable in water. <ref name="Klos">Kloske, M., & Witkiewicz, Z. (2019). Novichoks – The A group of organophosphorus chemical warfare agents. Chemosphere, 221, 673. doi:10.1016/j.chemosphere.2019.01.054</ref> These chemicals are illegal but it does not stop people from illegally synthesizing these agents. <ref name="Gardiner">Gardiner, B. (n.d.). The Chemical Weapons Detectives. Popular Science, 290(5), winter 2018, 88</ref><br />
<br />
[[Media:Novichok_synthesis.png|Image of Synthesis]]<br />
<br />
== '''How it works''' ==<br />
Nerve agents are effective due to their interaction with acetylcholinesterase . This is significant because the body uses this enzyme to remove acetylcholine as it can be dangerous if it builds up in the body. Without the removal of acetylcholine, the muscles are continually contracting and spasming. Nerve agents work by interrupting communication between nerves and muscles or communication between nerves in the brain. <ref name="cotton">Cotton, S. (2018). Nerve Agents: What Are They and How Do They Work? American Scientist, 106(3), may/june 2018, 138. doi:10.1511/2018.106.3.138</ref> These agents work within minutes of a person being exposed to them and symptoms appear right away. <br />
When using X-ray crystallography to try and understand the structure of sarin, it was found that the isopropyl component becomes a closed conformation in order to shield the phosphorus atom so that it cannot be attacked . This was found in both human and nonhuman subjects and so it was determined that this was due to the preferred conformation being closed rather than being due to the crystal packing. <ref> Allgardsson, A., Berg, L., Akfur, C., Hörnberg, A., Worek, F., Linusson, A., & Ekström, F. J. (2016). Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6. Proceedings of the National Academy of Sciences, 113(20), 5516. doi:10.1073/pnas.1523362113</ref> This is significant as it gives researchers insight as to how a nerve agent protects itself from other chemicals in the body that may try to attack it.<br />
<br />
== '''Binding to Acetylcholinesterase''' ==<br />
Nerve agents bind to acetylcholinesterase at one site, the active center which is a narrow gorge on the enzyme. <ref name="Stone"> Stone, R. (2018, September 25). How to defeat a nerve agent. Retrieved from https://www.sciencemag.org/news/2018/01/how-defeat-nerve-agent. </ref> Nerve agents contain a phosphorus group that binds to the hydroxyl group that is located on this enzyme. This is the location where acetylcholine usually binds, therefore these agents act as a competitive inhibitor of acetylcholine. The body will need to synthesize more enzymes so that it does not build up, but since the human body cannot do it fast enough, most people who are exposed to a nerve agent will die. The main reason that nerve agents are so deadly is that when the phosphorus group of the agent binds to they hydroxyl group, it forms a covalent bond, with the serine residue, so strong that it cannot be broken <br />
<br />
== '''Current Treatment''' ==<br />
Due to the real possibility of an attack using these deadly chemicals, researchers are working on finding antidotes or treatments that can save a person’s life or even just delay death so that researchers have more time to find a way to cure this. The main focus for these treatments is to get the nerve agent to release the acetylcholinesterase, even if the reaction mechanism is unknown. The United States Army requires its soldiers to carry an anticonvulsant called Diazepam with them in case of a nerve agent attack. However, there is a push to carry midazolam which acts faster than what is currently used. <ref name="Stone"> Stone, R. (2018, September 25). How to defeat a nerve agent. Retrieved from https://www.sciencemag.org/news/2018/01/how-defeat-nerve-agent. </ref> When a victim is being treated in a hospital, a mixture of two chemicals are used to treat the poisoning. These are Atropine, which blocks the acetylcholine receptors, and a reactivator, which is used to restore acetylcholinesterase to its original function, therefore negating the effects of a nerve agent. <ref>Nerve Agents Guide. (n.d.). Retrieved from https://www.osha.gov/SLTC/emergencypreparedness/guides/nerve.html</ref><br />
More research is being done on treatments that allow an oxime to become neutral so that it can cross the blood-brain barrier, which is where a nerve agent does most of its work. <ref name="Stone"> Stone, R. (2018, September 25). How to defeat a nerve agent. Retrieved from https://www.sciencemag.org/news/2018/01/how-defeat-nerve-agent. </ref> <br />
<br />
== '''Conclusions''' ==<br />
While the chemical structures of some of these nerve agents are not known due to the synthesis of these chemicals being illegal, there are proposed structures since researchers know the essential chemical groups that are a part of nerve agents. Due to the unknown structures, it is difficult to synthesize antidotes to these nerve agents, but researchers can try to find treatments that will work without knowing the structure. The threat of a nerve agent attack is a possibility in our world today and so it is essential to understand how these agents affect the body so that measures can be taken to keep the public as safe as possible. <br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3034439User:Jason Telford/Telford Sandbox 12019-04-29T13:56:43Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
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<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen>PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
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This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3034437User:Jason Telford/Telford Sandbox 12019-04-29T13:55:47Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen><PMID: 16214139 </ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3034436User:Jason Telford/Telford Sandbox 12019-04-29T13:54:41Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
<br />
This is a reference to a cockroach allergen <ref name=allergen><PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3034435User:Jason Telford/Telford Sandbox 12019-04-29T13:54:13Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
This is a reference to a cockroach allergen <ref name=allergen><PMID: 26706467</ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3034434User:Jason Telford/Telford Sandbox 12019-04-29T13:53:45Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
This is a reference to a cockroach allergen <ref name=allergen><PMID: 26706467/ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==<br />
<references/></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3034433User:Jason Telford/Telford Sandbox 12019-04-29T13:53:19Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
This is a reference to a cockroach allergen <ref name=allergen><PMID: 26706467/ref><br />
<br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene><br />
==references==</div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3034432User:Jason Telford/Telford Sandbox 12019-04-29T13:52:38Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page.<br />
This is a reference to a cockroach allergen <ref name=allergen><PMID: 26706467/ref><br />
and this is a repeat of that reference<ref name=allergen/><br />
<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3033551User:Jason Telford/Telford Sandbox 12019-04-24T14:02:59Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
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<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
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This is a test page<br />
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This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
Showing <scene name='46/464795/Milkprotein/2'>overlap</scene> of OLA and EIC<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page<br />
each new scene can take a bit to show up when clicked- be patient<br />
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<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
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<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
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<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
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<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
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We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
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This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
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A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3029987User:Jason Telford/Telford Sandbox 12019-04-22T13:25:56Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
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<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG<br />
<br />
A test scene to show scene <scene name='46/464795/Enh_zoom/1'>transitions</scene></div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3022590User:Jason Telford/Telford Sandbox 12019-04-04T18:37:12Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/3'>TextToBeDisplayed</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG</div>Jason Telfordhttps://proteopedia.org/index.php?title=User:Jason_Telford/Telford_Sandbox_1&diff=3022588User:Jason Telford/Telford Sandbox 12019-04-04T18:34:19Z<p>Jason Telford: </p>
<hr />
<div>Insert pdb after this<br />
<br />
<Structure load='1enh' size='500' frame='true' align='right' caption='Insert caption here' scene='Scene' /><br />
<br />
This is a test page<br />
<br />
This scene is of Diploptera punctata <scene name='46/464795/Milkprotein/1'>protein</scene>, aka cockroach milk. <br />
''blah <scene name='46/464795/Scene99/1'>blah</scene> blah''<br />
<br />
Load Scene Authoring tools<br />
Load molecule (start from scratch each time)<br />
Make selections, change view for each selection (under style)<br />
you might tick off 'show only selected residues'<br />
save scene (give it a logical number), newly saved scenes are incremented (scene1/1, scene1,2, scene1,3) automatically- I think<br />
close scene authoring tools<br />
save page<br />
each new scene can take a bit to show up when clicked- be patient<br />
<br />
<br />
<scene name='46/464795/1enhscenetest/1'>1enhscenetest</scene><br />
<br />
<br />
<scene name='46/464795/Scene1/6'>TextToBeDisplayed</scene><br />
<br />
<scene name='46/464795/Scene_2/1'>Backbone in trace, residue 52 in CPK</scene><br />
<br />
<scene name='46/464795/Scene_2/2'>backbone in strand, red</scene><br />
<br />
We are going to put this <scene name='46/464795/Scene2/1'>scene that shows 1wq5 in cartoon depiction</scene> in the middle of a sentence!<br />
<br />
This is test <scene name='46/464795/Test_scene6/1'>scene</scene> 6, 1ARG</div>Jason Telfordhttps://proteopedia.org/index.php?title=Abrin&diff=2988368Abrin2019-01-07T19:02:55Z<p>Jason Telford: </p>
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<div><scene name='77/778334/Alpha_chain/1'></scene><br />
==Abrin==<br />
<StructureSection load='1ABR' size='340' side='right' caption='Glycosylated abrin (PDB code [[1abr]])' scene=''><br />
== Introduction ==<br />
''Abrus precatorius'' (or rosary peas) contain the protein '''abrin'''. Rosary peas are red and oval-shaped with a black edge towards one end. In some cultures, they are used to make beaded jewelry. Abrin can exhibit beneficial uses for medical research, but it can also be destructive if it directly enters an organism’s body because of its toxic properties. <br />
== Structure ==<br />
Abrin is referred to as a type-2 ribosome-inactivating protein (RIP). The protein contains two chains:<scene name='77/778334/A_chain/1'> α</scene> and <scene name='77/778334/Abrin_b_chain/1'>β</scene> which are connected by a disulfide bond. Both of the chains are <scene name='77/778334/Water/1'>water soluble</scene>. The water molecules hydrolyze the N-C glycosidic bond. The β chain allows the α chain to enter a cell because it attaches to the carbohydrate receptors. The β is composed of the following amino acids: Ile-Val-Glu-Lys-Ser-Lys-Ile-Ser-Ser-Ser-Arg-Tyr-Glu-Pro-Thr. The α chain is known as an N-glycosidase <ref name="Yu">DOI:10.1093/abbs/gmw023</ref>. Once the α chain is in a cell, the chain removes adenine bases and links to the 28S rRNA<ref name="Wooten">DOI: 10.1007/s13181-013-0377-9</ref>. The attachment causes the ribosome to be incompetent when trying to connect to an elongation factor leading to an inhibition of protein synthesis.<br />
== Medical Potential ==<br />
Abrin has remained a key interest in a treatment for cancer. In one study, scientists wanted to see if abrin would decrease the number of colon cancer cells in vitro and vivo models. One experiment showed that purified abrin can influence cell cycle arrest and apoptosis. The study states abrin “significantly increased p21 mRNA expression and decreased PCNA, cyclin B1, Ki67 mRNA expression" <ref name = "Yu"/> which induced a halt in cell growth. For example, p21 can inhibit the CDK2 which regulates the checkpoints of the cell cycle; meaning, if there is an increased level of p21, more CDK2s will be affected. It also stated that abrin can enhance Bcl-2 which causes cytochrome c to be released. With this data, the study suggested that abrin could act as an anticancer treatment for colon cancer; however, a further experiment would have to test abrin’s impact on other cells such as erythrocytes, neurons, or dendritic cells <ref name = "Wooten"/>.<br />
== Negative Effects/Treatment ==<br />
If an entire rosary pea is ingested, the person will have mild to no symptoms. However, if the shell breaks, the effects of abrin will be released. Abrin is able to induce apoptosis and cell cycle arrest, ingestion of the protein abrin is lethal. If abrin is consumed or inhaled into the human system, symptoms will include difficulty breathing, vomiting, diarrhea, fever, and organ failure. The lethal dose of abrin is 0.1-1 micrograms <ref> doi:10.12659/AJCR.892917</ref> Someone who has been poisoned by abrin will need fluids, a ventilator, and activated charcoal. Another method for suppressing the symptoms of abrin poisoning is to use CRRT and hemoperfusion. CRRT purifies the blood for a day’s duration. CRRT can destroy toxins up to 1-20kDa in size. Hemoperfusion, which is more effective than CRRT can filter the blood and cause a decrease in levels of the toxin. While these methods have the potential for successfully clearing a toxin, it is still essential for those that have been exposed to a toxin to seek medical help, fast and efficiently<ref>doi:10.1097/MD.0000000000007423</ref>.<br />
== Bioterrorism/Prevention ==<br />
Abrin is very similar to ricin because of its structure and functions. While abrin hasn’t been used for bioterrorism, there have been multiple occasions of ricin misuse. For example, in London of 1978, Georgi Markov was attacked by a man with an umbrella, who was employed by the Bulgarian secret service. The umbrella was designed to release a piece ricin which ended up lodging into Markov's skin. Markov died three days after being exposed to the toxin of ricin <ref>"Facts About Abrin.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 18 Nov. 2015, emergency.cdc.gov/agent/abrin/basics/facts.asp.</ref>. Other acts of bioterrorism have included envelopes with the exposure to ricin being mailed to government officials including the President. Since then a vaccine has been created to suppress the effects of ricin poisoning. However, there is still a potential for the use of abrin in a bioterrorism attack. As of right now, they are in development of a vaccine and have learned in one study that a rATB vaccine will possibly rid the symptoms of abrin poisoning<ref>doi:10.1080/21645515.2015.1008879</ref>.<br />
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</StructureSection><br />
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==3D structures of abrin==<br />
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} <br />
<br />
[[1abr]], [[5z37]] – IlAbr-A – Indian licorice<br /><br />
[[5z3i]] – IlAbr-A + adenine<br /><br />
[[5z3j]] – IlAbr-A + nicotinamide<br /><br />
== References ==<br />
<references/><br />
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[[Category:Topic Page]]</div>Jason Telford