Proteopedia - User contributions [en]

User:Mark Macbeth/Sandbox13

2025-04-10T14:21:00Z

Mark Macbeth:

=PET hydrolase=
<StructureSection load='4eb0' size='350' side='right' caption='Insert caption here' scene='10/1075193/Wild_type_pet_hydrolase/2'>
==Introduction==
==Environmental Issues==
Pollution is one of the largest environmental issues facing our globe today. It is estimated that there is 359 million tons of plastic waste, excluding all other forms of material waste, produced annually around the world. Of this plastic waste, 150-200 million tons of it ends up sitting in landfills or ends up as pollution in our natural environments. The most common form of plastic waste is [https://en.wikipedia.org/wiki/Polyethylene_terephthalate poly-ethylene terephthalate], or PET, which has an annual production accumulation of six billion pounds made, generally in the form of soft drink containers and plastic water bottles. It is recycled in some aspects with around only 10% recycled. The methods that are currently being implemented are not conducive on a global scale.
==Current Plastic Recycling Methodology==
Strides have been taken to find a method by which PET plastics can be recycled, but many of the current employments are not conducive on a large global scale. Enzymes, specifically cutinases and hydrolases, have been a major turning point in progression of recycling. However, many of the ones studied face the issue of having a low thermal stability. PET plastics have to be broken down and/or melted at temperatures around or above 70 degrees Celsius, which the current enzymes studied cannot maintain their structure and will denature under those conditions. Some of the enzymes also do not fully break down the plastics into their original starting materials, which can be reused/recycled to make new plastic products. If the plastics cannot be fully broken down, then they cannot be recycled.
One alternative among the population of cutinases and hydrolases exists, though, that can complete the goal of recycling PET plastics at and above its transition temperature: leaf compost cutinase, or LCC. In both its wild-type and mutated versions, the LCC has become a revolutionary enzyme that could work towards the progression of ending our global environmental recycling issues.
==Structure==
==Alpha-Beta Hydrolase Family==
Leaf-branch compost bacterial cutinase features an [https://en.wikipedia.org/wiki/Alpha/beta_hydrolase_superfamily alpha-beta hydrolase fold] as its catalytic domain. The alpha-beta hydrolase fold features a chymotrypsin-like catalytic triad with a conserved histidine, a hydrophobic binding pocket, and an oxyanion hole. The primary structure contains a nucleophilic motif of G-X-Nu-X-G. The flanking glycines allow the nucleophilic region of the active site to form a tight loop called the nucleophilic elbow. Some alpha-beta hydrolase enzymes have the motif HX*4D, which allows them to exhibit acyltransferase activity. Alpha-beta hydrolase enzymes have a wide range of functions including proteolysis, signal transduction, and lipid metabolism.
==Overall Topology==
Leaf-branch compost bacterial cutinase, LCC, is a part of the [https://en.wikipedia.org/wiki/Serine_hydrolase serine hydrolase] family. It is a monomer that contains a total of 258 amino acid residues, with an amphipathic structure. It has a <scene name='10/1075191/Overall_topology/1'>secondary structure</scene> made up of alpha helices and beta turns, which correlate to the alpha-beta hydrolase family. The active site consists of a <scene name='10/1075191/Active_site_overall_topology/5'>catalytic triad</scene>, which is a common feature among serine hydrolases. Compared to other serine hydrolases and cutinases studied for plastic degradation, the LCC proved to be 33x more efficient.
==Active Site==
==Structure==
The active site contains a <scene name='10/1075193/Hydrophobic_binding_pocket/6'>hydrophobic binding pocket</scene> which makes [https://en.wikipedia.org/wiki/Pi-stacking aromatic pi-stacking] and [https://en.wikipedia.org/wiki/Van_der_Waals_force Van der Waals interactions] with the aromatic rings in the PET ligand. Add a table with residues+monomers. There is currently no available structure of LCC with the PET ligand bound to it so the ligand position has been approximated in this model.
{| class="wikitable" style="width: 50%;"
|+ Table 1. Residues in contact with PET substrate. The table shows the 15 amino acid residues in the first contact shell with the PET substrate. Residues are sorted into columns based on which monomer they are interacting with. Monomers are labeled consistently with how they were labeled in the Tournier et al. article.
|-
! Site -2
! Site -1
! Site +1
|-
| Y95
| G94
| S101
|-
| F125
| T96
| F243
|-
| Y127
| H164
| N246
|-
| M166
| S165
|
|-
| W190
| D210
|
|-
| A213
| V212
|
|-
|
| H242
|
|}

==Mechanism==
The mechanism involves a proton relay by the <scene name='10/1075193/Cat_triad_ligand/1'>catalytic triad</scene>, making the catalytic S165 a good nucleophile. S165 attacks the carbonyl carbon in the -1 monomer of the PET Polymer, forming a tetrahedral intermediate (insert scene - keep old numbering?). The pi electrons move onto the carbonyl oxygen, creating an oxyanion which is stabilized by the <scene name='10/1075193/Oxyanion_hole/2'>oxyanion hole</scene>, consisting of the backbone amide nitrogens of Y95 and M166. Then, the leaving group oxygen on the -2 monomer is protonated by H242, which is also a part of the catalytic triad (insert scene?). This facilitates the reformation of the carbonyl group upon collapse of the oxyanion and the severing of the scissile bond (insert scene).
In a second step, a water molecule is deprotonated by H242 and D210, allowing it to nucleophilically attack the carbonyl carbon, forming a tetrahedral intermediate and an oxyanion that is stabilized by the same <<scene name='10/1075193/Oxyanion_hole/2'>oxyanion hole</scene>. H242 protonates the leaving group oxygen of S165, allowing the reformation of the carbonyl and the severing of the covalent bond to serine. The -1 monomer is released from the enzyme, and the protons are reset for further catalysis.
[[Image:PET_hydrolase_Mechanism.jpeg|400 px|left|thumb|Figure Legend]] need higher quality image of this
==Mutations==
Researchers have been investigating various mutations of PET hydrolase to enhance its catalytic ability. One group of researchers, Tournier et. al., have made mutations in the PET hydrolase active site. They identified the key residues involved in the catalytic mechanism by using a model of the <scene name='10/1075190/Ligand/2'>PET substrate</scene> onto the enzyme. The site, mainly a hydrophobic pocket, contained 11 residues targeted for mutagenesis. From this, they identified that the majority of enzymes' specific activity went down; however, the mutation of the F243 to either isoleucine or tryptophan increased specific activity. Four target mutations introduced into the PET Hydrolase by Tournier et. al. demonstrated improved catalytic efficiency and thermal stability compared to its wild-type structure.
==F243I/W Mutations==
Mutating the active site <scene name='10/1075193/F243/3'>F243</scene> to <scene name='10/1075193/F243i/4'>F243I</scene> (in the ICCG mutant) and <scene name='10/1075193/F243w_mutant/2'>F243W</scene> (in the WCCG mutant) resulted in a percent gain of specific activity of 127.5% and 118.4% respectively. More information here.
==D238C/S283C Mutations==
A disulfide bond was put into the structure of the LCC by mutating <scene name='10/1075191/Wild_type_d238_and_s283/3'>wild type D238/S283</scene> into cysteine disulfide scene (recopy scene link). The disulfide bond specifically replaced those residues due to the triplet acidic residue sequence E208/D238/S283 serving as a common divalent metal binding site in other cutinase enzymes. This allowed the researchers to compare the activity of the disulfide bond mutation’s activity and stability to that of the cutinases with additional metal ions that showed increased activity and stability. (Disulfide bonds are also comparable to metal cations in terms of enhancing protein structural thermal stability.) The disulfide bond proved true to enhance the thermal stability of the PET hydrolase, increasing its melting temperature to 94.5 degrees Celsius to that of the wild-type’s 84.7 degree Celsius thermal stability. A tradeoff with catalytic activity occurred, though, decreasing enzymatic activity by 28% compared to the wild type. The thermal stability seemed to be more important than activity rates if the LCC still did its intended function.
==Y127G Mutation==
A <scene name='10/1075191/Mutation_y127_to_g127/1'>glycine mutation</scene> was introduced to residue the <scene name='10/1075191/Wild_type_y127/1'>wild type Y127</scene>. The main effect of this mutation was that it showed an increase in melting temperature, but with no effect on depolymerization of the PET substrates compared to the wild type. With the addition of the glycine, the ICC/WCC mutations showed a similar or higher specific activity with a higher melting point compared to the wild type (9.3 to 13.4 degrees Celsius higher). Distances between the catalytic serine (S165) and the ligand where the scissile bond is located, as well as with the catalytic histidine (H242), decreased to enhance catalytic efficiency of LCC with new covalent interactions facilitated.
==Glycosylation==
<scene name='10/1075191/All_glycosylation_sites/5'>Glycosylation sites</scene> were introduced in a research study completed by Abhihit N. Shirke and others with the initial intention of inducing aggregation in the leaf branch cutinase / PET hydrolase wild-type. <ref name="Shirke">PMID:29328676</ref> Glycosylation, as a general tool, is introduced into a protein to improve conformational stability. The specific type used in this study was N-linked side chain alteration. This means that the glycosylation sites were selected based on a starting asparagine residue followed by the sequence N-X-S or N-X-T, where X stands for any of the twenty amino acids except proline. <ref name="Imperiali">PMID:10600722</ref> This is implemented specifically because it allows for a better ability to choose the mutation sites. The first glycosylation site followed the N-T-S pattern with <scene name='10/1075191/First_glycosylation_site/5'>residues 197-199</scene>. The second was <scene name='10/1075191/Second_glycosylation_site/4'>residues 239-241</scene> with an N-A-S pattern, located nearest to the active site. The final was <scene name='10/1075191/Third_glycosylation_site/4'>residues 266-268</scene>, exhibiting a N-D-T sequence. <ref name="Shirke">PMID:29328676</ref> With the combination of these glycosylation sites (without any other mutagenesis introduced to the enzyme), an overall 10-degree Celsius higher thermal stability was exhibited compared to the wild-type, with the structure of the modified PET hydrolase three times more stable. Catalytic efficiency also improved at the enzyme's known melting temperature. Even though the target point of introducing glycosylation sites was to induce aggregation in the PET hydrolase, depletion of aggregation was exhibited. The glycosylated protein took twice as long to unfold compared to the wild-type. For comparison, the threshold of 80 degrees Celsius was where the major difference in kinetic activity occurred: 85% of the glycosylated hydrolase maintained its catalytic activity, whereas the wild-type only had 50% of it working at the same temperature.<ref name="Shirke">PMID:29328676</ref> The first and third sites showed these trends both together and on their own as the only glycosylation sites, but the second one nearest the active site showed no change when glycosylated on its own when compared to the wild type. <ref name="Shirke">PMID:29328676</ref>
==Biochemical Results==
==Improved Thermal Stability==
Thermal stability is very important for enzyme-catalyzed PET degradation because the reaction must take place above the transition temperature of PET(70ºC), which allows the substrate to have optimal flexibility to fit into the active site. The disulfide bridge mutation raises the melting point of the enzyme from 84.7ºC to 94.5ºC.
==Depolymerization Efficiency of Mutant LCCs==
Both the ICCG and WCCG mutants designed by Tournier et al. exhibited a greater depolymerization efficiency than the wild type. The wild type LCC reached 53% depolymerization in 20 hours while both the ICCG and WCCG mutants reached 90% depolymerization in 10.5 hrs and 9.3 hrs respectively. Should this be discussed like a scientific article with these things in the conclusion or should these be discussed in the prior sections and the conclusions just talk about implications of the discovery for recycling?
==Enhanced Catalytic Efficiency==
The ICCG and WCCG mutations constructed by Tournier et al. showed a return to the wild type activity and beyond. The tryptophan mutation showed a 122% increase in catalysis, with an increased ability to sustain its structure at temperatures 6.2 degrees higher than the wild type (84.7 degrees Celsius). The isoleucine mutation showed a 2% decrease in activity compared to the wild type, but a thermal stability increase by 10.1 degrees Celsius.
==Conclusions==
==Implications for Plastic Recycling==
Information here

=References=
<references/>
</StructureSection>
=Student Contributors=
*Georgia Apple
*Emily Hwang
*Anjali Rabindran

User:Mark Macbeth/Sandbox14

2025-04-08T18:26:10Z

Mark Macbeth:

=CH462 Thyroid Hormone GPCR=
<StructureSection load='Edited_7utz' size='350' frame='true' side='right' caption='The thyrotropin receptor with TSH bound. TSHR is shown in dark blue with TSH (light green) bound. The receptor is bound to its G-protein with the various subunits of the G-protein shown in pink, red, turquoise, and yellow. PDB:[https://www.rcsb.org/structure/7UTZ 7UTZ]' scene='95/952709/Initial_scene_with_edited_7utz/7'>

== Introduction ==
[[Image:surface TSHR.png|400 px|right|thumb|Figure 1. TSHR with TSH bound. The extracellular and transmembrane domains of the GPCR are shown in green, the hinge region in cyan, and thyrotropin bound in magenta. PDB:[https://www.rcsb.org/structure/7UTZ 7UTZ]]]
[https://en.wikipedia.org/wiki/Thyroid_hormones Thyroid hormones] exercise essential functions related to activity of thyroid cells as well as metabolic processes and oxygen consumption<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. The initiation of the synthesis and release of these hormones is caused by the glycoprotein, thyroid stimulating hormone <scene name='95/952708/Tsh_7t9i/2'>(TSH)</scene>, which is released by the anterior pituitary gland<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. The release of TSH from the anterior pituitary is simulated by thyroid-releasing hormone (TRH) which is released by the hypothalamus. When stimulated by TSH, the thyroid gland will produce and release the the thyroid hormones T4 and T3. T3 is the "active form" of the hormone, however it accounts for only 20% of the thyroid hormone that is released after stimulus by TSH. The T4 that predominates in release from the thyroid will be converted to T3 in the bloodstream. High levels of T3 and T4 can negatively regulate the release of TSH from the anterior pituitary, constituting a negative feedback loop <ref name="Pirahanchi et al.">Pirahanchi Y, Toro F, Jialal I. Physiology, Thyroid Stimulating Hormone. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499850/</ref>. The thyrotropin receptor <scene name='95/952709/Initial_scene_with_edited_7utz/7'>(TSHR)</scene> is a [https://www.nature.com/scitable/topicpage/gpcr-14047471/ G-protein coupled receptor] on the surface the thyroid gland cells (Figure 1). TSHR is responsible for binding TSH and transduces signal to initiate synthesis and release of thyroid hormones. In addition to TSH, autoantibodies may also bind to TSHR causing inhibition or activation of its desired function.<ref name="Duan et al.">PMID:35940204</ref><ref name="Kohn et al.">Kohn LD, Shimura H, Shimura Y, Hidaka A, Giuliani C, Napolitano G, Ohmori M, Laglia G, Saji M. The thyrotropin receptor. Vitam Horm. 1995;50:287-384. doi: 10.1016/s0083-6729(08)60658-5. PMID: 7709602.</ref> The resulting misregulation of thyroid hormone levels is the cause of many disorders related to [https://www.endocrineweb.com/conditions/thyroid/hyperthyroidism-vs-hypothyroidism hypo- or hyperthyroidism]. Thus, understanding the signaling of synthesis and release of these hormones will have applications in treating [https://www.hopkinsmedicine.org/health/conditions-and-diseases/disorders-of-the-thyroid thyroid hormone disorders]<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>.
== Structure ==
=== Active and Inactive Form ===
[[Image:Finalmorphpic2.png|450 px|right|thumb|Figure 2: Inactive form of the thyrotropin receptor shown in blue (PDB:[https://www.rcsb.org/structure/7T9M 7T9M]). Active form of the thyrotropin receptor shown in green (PDB:[https://www.rcsb.org/structure/7T9I 7T9I]).]]
TSHR exists in dynamic equilibrium between two states: active and inactive (Figure 2). In the active form, the extracellular portion is rotated 55° away from the cell membrane. TSH will bind and keep the active state in the up position as a result of clashes between bound TSH and the cell membrane.<ref name="Faust" />. <scene name='95/952708/Tsh_7t9i/5'>Glycolysations of an N52 residue</scene> on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene> cause this clash.
===Structural Overview===
The thyrotropin receptor has an extracellular domain (ECD) that is composed of a <scene name='95/952709/Lrrd_real/3'>leucine rich repeat domain (LRRD)</scene> as well as a hinge region. The <scene name='95/952709/Hinge_region_real/6'>hinge region</scene> links the ECD to the seven transmembrane helices <scene name='95/952709/7tm_helices/5'>(7TM domain)</scene>, which span from the ECD to the intracellular loops <ref name= "Keinau et al.">Kleinau, G., Worth, C. L., Kreuchwig, A., Biebermann, H., Marcinkowski, P., Scheerer, P., & Krause, G. (2017). Structural–functional features of the thyrotropin receptor: A class A G-protein-coupled receptor at work. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00086</ref>. Thyrotropin binding causes a conformational change in the ECD that is transduced through the transmembrane helices. In the active state, the ECD is in the "up" position, while in the inactive state, the ECD is in the "down" state, closer to the cell membrane. A "push-pull" mechanism is proposed for the ECD's conformational change between active and inactive states. In the "push" model, TSH binds to the receptor and sterically clashes with the cellular membrane, forcing the ECD up away from the membrane. In the pull model, a short α-helix interacts with TSH to pull the ECD up. The active (up) form of the ECD causes a conformation shift in the TMD which causes differential interactions with a heterotrimeric <scene name='95/952709/G_protein/2'>G-protein</scene>, initiating intracellular signaling<ref name="Duan et al.">PMID:35940204</ref>.
=== Leucine Rich Repeats ===
The Leucine Rich Repeat Domain (LRRD) is part of the <scene name='95/952708/Tshr_chainr_ecd/1'>ECD</scene> of TSHR and contains <scene name='95/952707/Lrr/5'>10-11 Leucine Rich Repeats</scene>. A unique feature of this region is that it is composed entirely of β-pleated sheets. These β-pleated sheets of the LRRD provide a concave binding surface for TSH, including the residues <scene name='95/952707/Interactions_with_thyrotropin/4'>K209 and K58</scene> <ref name="Duan et al.">PMID: 35940204</ref>. These interact with <scene name='95/952707/Interactions_with_thyrotropin/4'>N91 and E98</scene> in the seatbelt region of TSH forming a salt bridge and assisting in binding TSH <ref name="Faust">PMID: 35940205</ref>. This interaction is specific to TSH and TSHR. When other agonists or antagonists bind to the receptor, the change in conformation is a result of different residues interacting, as explained later in the page. The LRRD acts as a probe to receive information from the extracellular environment.
===Hinge Region and P10 Peptide===
The <scene name='95/952709/Hinge_region_real/5'>hinge region</scene> is a scaffold for the attachment of the LRRD to the 7TMD. The hinge region also impacts TSH binding potency and intracellular cyclic adenosine monophosphate (cAMP) levels, mediated by the activation of the GPCR<ref name="Mizutori et al.">Yumiko Mizutori, Chun-Rong Chen, Sandra M. McLachlan, Basil Rapoport, The Thyrotropin Receptor Hinge Region Is Not Simply a Scaffold for the Leucine-Rich Domain but Contributes to Ligand Binding and Signal Transduction, Molecular Endocrinology, Volume 22, Issue 5, 1 May 2008, Pages 1171–1182, https://doi.org/10.1210/me.2007-0407</ref>. The hinge region's <scene name='95/952709/Hinge_helix_rotation/2'>hinge helix</scene> interacts with the <scene name='95/952709/P10_peptide_region/3'>p10 peptide</scene> through <scene name='95/952709/Disulfides/1'>disulfides</scene>. The p10 peptide is a conserved sequence that spans from the last β sheet of the LRRD to the first transmembrane helix (TM1) and is an intramolecular agonist for conformational shifts in the 7TMD helices<ref name="Faust et al.">Faust, B., Billesbølle, C.B., Suomivuori, CM. et al. Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature 609, 846–853 (2022). https://doi.org/10.1038/s41586-022-</ref>. The disulfides between the LRRD, the hinge helix, and the p10 are critical to TSH signaling as they transduce signal from the ECD through the hinge helix to the p10 peptide. The upward movement of the LRRD, caused by TSH binding, will cause rotation of the hinge helix. The subsequent movement of the p10 peptide leads to movement of the transmembrane helices, which will cause activation of the G-protein. In addition to activation, the hinge region plays an important role in tightly binding TSH. Residues 382-390 of the hinge region adopt a short helix containing two key residues. Y385 from TSHR is buried into a hydrophobic pocket of TSH. D386 from the receptor forms a salt bridge with R386 of the hormone. <scene name='95/952709/Binding_interactions_hinge/2'>Interactions</scene> that assist in the stable binding of TSH to TSHR allow more potent activation of the receptor<ref name="Duan et al.">PMID:35940204</ref>. Even with these key functions, the hinge region itself is not absolutely required for receptor activation<ref name="Faust et al.">Faust, B., Billesbølle, C.B., Suomivuori, CM. et al. Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature 609, 846–853 (2022). https://doi.org/10.1038/s41586-022-</ref>. The hinge region functions as a point of attachment to the 7TMD for the LRRD, and its ability to rotate allows for LRRD shifts between up (active state) and down (inactive state) positions. The interactions that the hinge helix makes with the LRRD and p10 act as an important communication medium between the ECD and an intramolecular agonist directly effecting conformational shifts in the 7TMD.
===7 Transmembrane Helices===
The ECD of TSHR is anchored to the membrane through seven transmembrane helices (7TMD), characteristic of GPCRs. Conformational changes in the 7TMD activate intracellular G-protein signaling<ref name= "Keinau et al.">Kleinau, G., Worth, C. L., Kreuchwig, A., Biebermann, H., Marcinkowski, P., Scheerer, P., & Krause, G. (2017). Structural–functional features of the thyrotropin receptor: A class A G-protein-coupled receptor at work. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00086</ref>. Once TSH binds, conformational changes to the p10 peptide are transmitted to the 7TMD. Specifically, hinge helix rotation causes the displacement of the p10 peptide that allows the <scene name='95/952709/Helix_7_of_7tmd/2'>seventh transmembrane helix (TM7)</scene> to migrate towards the center of the 7TMD, increasing van Der Waals contacts. Additionally, K660 of TM7 forms a stabilizing <scene name='95/952709/Helix_7_and__p10_interaction/8'>ionic interaction</scene> with E409 of the p10 region. Hinge helix movement also rearranges Y279 relative to I486 on the neighboring <scene name='95/952709/Hinge_helix_ecl1/3'>extracellular loop 1 (ECL1) helix</scene>, which links two transmembrane helices and is located extracellularly. Substitution of these residues leads to substantial shifts in the activation of the thyrotropin receptor. Structurally guided mutagenic studies have shown that replacing isoleucine with a more sizeable phenylalanine decreases TSH signaling potency<ref name="Faust et al.">Faust, B., Billesbølle, C.B., Suomivuori, CM. et al. Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature 609, 846–853 (2022). https://doi.org/10.1038/s41586-022-</ref><ref name="Vlaeminck-Guillem et al.">Virginie Vlaeminck-Guillem, Su-Chin Ho, Patrice Rodien, Gilbert Vassart, Sabine Costagliola, Activation of the cAMP Pathway by the TSH Receptor Involves Switching of the Ectodomain from a Tethered Inverse Agonist to an Agonist, Molecular Endocrinology, Volume 16, Issue 4, 1 April 2002, Pages 736–746, https://doi.org/10.1210/mend.16.4.0816</ref>.The sixth transmembrane helix of TSHR moves outward from the center of the 7TMD to <scene name='95/952709/Helix_6_facilitation_of_g-pro/4'>facilitate α-helix 5</scene> of the α-subunit of the G protein (Gα)<ref name="Faust et al.">Faust, B., Billesbølle, C.B., Suomivuori, CM. et al. Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature 609, 846–853 (2022). https://doi.org/10.1038/s41586-022-</ref><ref name="Goricanec et al.">Goricanec, D., Stehle, R., Egloff, P., Grigoriu, S., Plückthun, A., Wagner, G., & Hagn, F. (2016). Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding. Proceedings of the National Academy of Sciences, 113(26). https://doi.org/10.1073/pnas.1604125113 </ref>. Gα is activated for intracellular signaling when GDP is exchanged for GTP and dissociates from the γ- and β-subunits of the G-protein (Gγ and Gβ) to bind with other target proteins. Activation of the Gα is caused by conformational shifts in the 7TMD and three intracellular loops which directly interact with the G-protein<ref name= "Keinau et al.">Kleinau, G., Worth, C. L., Kreuchwig, A., Biebermann, H., Marcinkowski, P., Scheerer, P., & Krause, G. (2017). Structural–functional features of the thyrotropin receptor: A class A G-protein-coupled receptor at work. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00086</ref>. These conformational shifts in transmembrane helices are the mechanism of changing interactions of the G-protein with the receptor.

== TSHR Agonists and Antagonists ==
Chemical [https://en.wikipedia.org/wiki/Agonist agonists] are found in many living systems and serve as a way to activate receptors or pathways that are necessary for a wide array of biological processes. Chemical [https://en.wikipedia.org/wiki/Receptor_antagonist antagonists] block or inhibit biological processes. Different types of agonists/antagonists exist within the body including hormones, antibodies, and neurotransmitters. The body naturally produces autoantibodies that can act as agonists and mimic the activating mechanism of the natural hormone leading to disease.<ref name="Miguel"> doi:10.1677/JME-08-0152</ref>.
===M22 Agonist===
<scene name='95/952707/M22_edited/1'>M22</scene> is a [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] that is produced by patients with [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease Graves' Disease]. In Graves' disease, autoantibodies mimic TSH function and cause thyroid overactivity. <ref name="Miguel"> doi:10.1677/JME-08-0152</ref>. Grave's Disease is an autoimmune disease that is a result of hyperthyroidism, where too much TSH is being produced. This disease [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease effects 1 in 100 Americans and especially women or people older than 30 years of age]. The M22 [https://en.wikipedia.org/wiki/Autoantibody autoantibody] activates TSHR by causing a membrane clash with the ECD and the cell membrane, keeping the TSHR in the active state by preventing the TSHR from rotating to the inactive state (Figure 3). M22 mimics TSH activation of TSHR, and is a potent activator for intracellular signaling. <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> Although M22 binds in a similar manner to TSH, M22 does not interact with the hinge region when bound to TSHR.<ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> These findings show that the hinge region is not necessary for the activation of TSHR, and leads to the discovery of other methods of activation. [[Image:Agonist pic.png|450 px|right|thumb|Figure 3: Agonist and antagonist drugs for activating or inactivating the TSHR protein. Here the membrane clashes are demonstrated on TSHR with different agonists attached. CS-17 is orange, TSH is purple, and M22 is blue in the figure. The TSHR protein is green and embedded in the protein.]]
===CS-17 Inverse Agonist===
<scene name='95/952708/Cs17/1'>CS-17</scene> is a [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] that acts as an inverse agonist for TSHR constitutive activity. <ref name= "Chen et al.">Chen, C.-R., McLachlan, S. M., & Rapoport, B. (2007). Suppression of thyrotropin receptor constitutive activity by a monoclonal antibody with inverse agonist activity. Endocrinology, 148(5), 2375–2382. https://doi.org/10.1210/en.2006-1754</ref>. An example of a disease caused by inverse agonists is [https://www.mayoclinic.org/diseasesconditions/hypothyroidism/symptomscauses/syc20350284#:~:text=Hypothyroidism%20happens%20when%20the%20thyroid,symptoms%20in%20its%20early%20stages hypothyroidism]. The most common cause of hypothyroidism is [https://www.mayoclinic.org/diseasesconditions/hypothyroidism/symptomscauses/syc20350284#:~:text=Hypothyroidism%20happens%20when%20the%20thyroid,symptoms%20in%20its%20early%20stages Hashimoto’s disease]. Without enough TSH to bind TSHR, the pathway remains inactive and thus metabolic processes are inhibited in this pathway. CS-17 interacts with the ECD of the TSHR protein on the
<scene name='95/952708/Cs17/2'>convex side</scene> of the LRRD, suppressing TSHR function by keeping the receptor in the inactive state (Figure 3). Clash of bound CS-17 with the cell membrane locks TSHR in the inactive form. This type of inhibition is uncommon and is a promising mechanism for future drug design and research to combat hypothyroidism.<ref name="Chen et al.">Chen, C.-R., McLachlan, S. M., & Rapoport, B. (2007). Suppression of thyrotropin receptor constitutive activity by a monoclonal antibody with inverse agonist activity. Endocrinology, 148(5), 2375–2382. https://doi.org/10.1210/en.2006-1754</ref>.

</StructureSection>
== References ==
<references/>

==Student Contributors==
*Jack Langford
*Veronika Bruetting
*Colin Flynn

File:Overlay8h7c3vjf fixchain fixMSE.pdb

2025-04-01T17:04:42Z

Mark Macbeth:

User:Mark Macbeth/Sandbox2

2025-04-01T14:20:27Z

Mark Macbeth:

<StructureSection load='6tht' size='350' side='right' caption='Sandbox 2' scene='78/784275/Pet_hydrolase/1'>

== Background ==
'''

== Significance ==

== Structure ==

=== Alternative Splicing Pathways ===

=== Autoregulation ===

</StructureSection>

== Additional Reading ==

For more information on the U2AF [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392075/ splicing factor].

== Relevance ==
As Sxl functions as a splicing repressor, it may give insight into the effects of varying mechanisms of alternate splicing both in flies and other species. Sxl may also lead to understanding of human alternative splicing factors. As an RNA binding protein, research regarding Sxl may contribute to the understanding of enzymes with RNA recognition motifs. The Sxl RNP motif of RBD1 is also conserved in the ELAV family of proteins<ref name="Handa"/>.

== References ==
<references/>

User:Mark Macbeth/Sandbox2

2025-04-01T14:11:38Z

Mark Macbeth:

<StructureSection load='6tht' size='350' side='right' caption='Sandbox 2' scene=''>

== Background ==
'''

== Significance ==

<scene name='78/784275/Ligand_no_h/1'>ligand rock</scene>

== Structure ==

=== Alternative Splicing Pathways ===

=== Autoregulation ===

</StructureSection>

== Additional Reading ==

For more information on the U2AF [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392075/ splicing factor].

== Relevance ==
As Sxl functions as a splicing repressor, it may give insight into the effects of varying mechanisms of alternate splicing both in flies and other species. Sxl may also lead to understanding of human alternative splicing factors. As an RNA binding protein, research regarding Sxl may contribute to the understanding of enzymes with RNA recognition motifs. The Sxl RNP motif of RBD1 is also conserved in the ELAV family of proteins<ref name="Handa"/>.

== References ==
<references/>

User:Mark Macbeth/Sandbox2

2025-04-01T14:09:02Z

Mark Macbeth:

<StructureSection load='6tht' size='350' side='right' caption='Sandbox 2' scene=''>

== Background ==
'''

== Significance ==

<scene name='78/784275/Ligand_no_h/1'>TextToBeDisplayed</scene>

== Structure ==

=== Alternative Splicing Pathways ===

=== Autoregulation ===

</StructureSection>

== Additional Reading ==

For more information on the U2AF [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392075/ splicing factor].

== Relevance ==
As Sxl functions as a splicing repressor, it may give insight into the effects of varying mechanisms of alternate splicing both in flies and other species. Sxl may also lead to understanding of human alternative splicing factors. As an RNA binding protein, research regarding Sxl may contribute to the understanding of enzymes with RNA recognition motifs. The Sxl RNP motif of RBD1 is also conserved in the ELAV family of proteins<ref name="Handa"/>.

== References ==
<references/>

File:6thtligandtest.pdb

2025-04-01T13:31:40Z

Mark Macbeth:

User:Mark Macbeth/Sandbox2

2025-04-01T13:08:20Z

Mark Macbeth:

<StructureSection load='6tht' size='350' side='right' caption='Sandbox 2' scene=''>

== Background ==
'''

== Significance ==

== Structure ==

=== Alternative Splicing Pathways ===

=== Autoregulation ===

</StructureSection>

== Additional Reading ==

For more information on the U2AF [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392075/ splicing factor].

== Relevance ==
As Sxl functions as a splicing repressor, it may give insight into the effects of varying mechanisms of alternate splicing both in flies and other species. Sxl may also lead to understanding of human alternative splicing factors. As an RNA binding protein, research regarding Sxl may contribute to the understanding of enzymes with RNA recognition motifs. The Sxl RNP motif of RBD1 is also conserved in the ELAV family of proteins<ref name="Handa"/>.

== References ==
<references/>

User:Mark Macbeth

2025-04-01T13:06:40Z

Mark Macbeth:

* Assistant Professor

* Department of Chemistry and Biochemistry

* Butler University

* Indianapolis, IN, USA

* Areas of Interest: Biochemistry, Structural Biology, RNA•Protein Interaction, Enzyme Catalysis

* Post-doctoral Howard Hughes Medical Institute and University of Utah School of Medicine

* Ph. D. Biochemistry and Molecular Biology, The University of Chicago

* B. S. Biological Sciences, University of Vermont

* [[User:Mark Macbeth/Sandbox1]]

* [[User:Mark Macbeth/Sandbox2]]

* [[User:Mark Macbeth/Sandbox10]]

* [[User:Mark Macbeth/Sandbox12]]

* [[User:Mark Macbeth/Sandbox13]]

* [[User:Mark Macbeth/Sandbox14]]

* [[Histone Modifying Enzymes]]

* [http://proteopedia.org/wiki/index.php/CH462_Butler CH462 Student Authored Pages]

* [http://proteopedia.org/wiki/index.php/Histone_Lysine_Methyltransferase_SET7/9 Histone Lysine Methyltransferase: SET7/9]

* [http://proteopedia.org/wiki/index.php/Histone_deacetylase_8_%28HDAC8%29 Histone deacetylase 8 (HDAC8)]

* [http://proteopedia.org/wiki/index.php/Histone_acetyltransferase_1-2_Complex_%28HAT1/2%29 Histone acetyltransferase 1-2 Complex (HAT1/2)]

* [http://proteopedia.org/wiki/index.php/Lysine-specific_demethylase_1_%28LSD-1%29 Lysine-specific demethylase 1 (LSD-1)]

User:Mark Macbeth

2025-04-01T13:05:52Z

Mark Macbeth:

* Assistant Professor

* Department of Chemistry and Biochemistry

* Butler University

* Indianapolis, IN, USA

* Areas of Interest: Biochemistry, Structural Biology, RNA•Protein Interaction, Enzyme Catalysis

* Post-doctoral Howard Hughes Medical Institute and University of Utah School of Medicine

* Ph. D. Biochemistry and Molecular Biology, The University of Chicago

* B. S. Biological Sciences, University of Vermont

* [[User:Mark Macbeth/Sandbox1]]

* [[User:Mark Macbeth/Sandbox10]]

* [[User:Mark Macbeth/Sandbox12]]

* [[User:Mark Macbeth/Sandbox13]]

* [[User:Mark Macbeth/Sandbox14]]

* [[Histone Modifying Enzymes]]

* [http://proteopedia.org/wiki/index.php/CH462_Butler CH462 Student Authored Pages]

* [http://proteopedia.org/wiki/index.php/Histone_Lysine_Methyltransferase_SET7/9 Histone Lysine Methyltransferase: SET7/9]

* [http://proteopedia.org/wiki/index.php/Histone_deacetylase_8_%28HDAC8%29 Histone deacetylase 8 (HDAC8)]

* [http://proteopedia.org/wiki/index.php/Histone_acetyltransferase_1-2_Complex_%28HAT1/2%29 Histone acetyltransferase 1-2 Complex (HAT1/2)]

* [http://proteopedia.org/wiki/index.php/Lysine-specific_demethylase_1_%28LSD-1%29 Lysine-specific demethylase 1 (LSD-1)]

User:Mark Macbeth/SandboxJustin

2025-03-18T19:59:53Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='6tht' size='350' frame='true' side='right' caption='ICCG PDB:6tht' scene=''>

==Introduction==
*[https://en.wikipedia.org/wiki/Cutinase Cutinase]
==Function==
==3-D Overview==
[[Image:11_res.png|400 px|right|thumb|Figure 1]]
==Active Site==
here is the <scene name='10/1075217/Cat_triad/1'>cat triad</scene>
===Mechanism===

== Structural highlights ==
This is my fav <ref name=”Tournier”>PMID:32269349</ref>

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.

</StructureSection>
== References ==

<references/>
==Student Contributors==
*Justin Chavez
*Hayden Vissing
*David Bogle

User:Mark Macbeth/SandboxJustin

2025-03-18T19:58:43Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='6tht' size='350' frame='true' side='right' caption='ICCG PDB:6tht' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxJustin'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Introduction==
*[https://en.wikipedia.org/wiki/Cutinase Cutinase]
==Function==
==3-D Overview==
[[Image:11_res.png|400 px|right|thumb|Figure 1]]
==Active Site==
here is the <scene name='10/1075217/Cat_triad/1'>cat triad</scene>
===Mechanism===

== Structural highlights ==
This is my fav <ref name=”Tournier”>PMID:32269349</ref>

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.

</StructureSection>
== References ==

<references/>
==Student Contributors==
*Justin Chavez
*Hayden Vissing
*David Bogle

User:Mark Macbeth/SandboxJustin

2025-03-18T19:57:05Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='6tht' size='350' frame='true' side='right' caption='ICCG PDB:6tht' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxJustin'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Introduction==
*[https://en.wikipedia.org/wiki/Cutinase Cutinase]
==Function==
==3-D Overview==
[[Image:11_res.png|400 px|right|thumb|Figure 1]]
==Active Site==
here is the <scene name='10/1075217/Cat_triad/1'>cat triad</scene>
===Mechanism===

== Structural highlights ==

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.

</StructureSection>
== References ==
<ref name=”Tournier”>PMID:32269349</ref>

<references/>
==Student Contributors==
*Justin Chavez
*Hayden Vissing
*David Bogle

User:Mark Macbeth/SandboxJustin

2025-03-18T19:55:42Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='6tht' size='350' frame='true' side='right' caption='ICCG PDB:6tht' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxJustin'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Introduction==
*[https://en.wikipedia.org/wiki/Cutinase Cutinase]
==Function==
==3-D Overview==
[[Image:11_res.png|400 px|right|thumb|Figure 1]]
==Active Site==
here is the <scene name='10/1075217/Cat_triad/1'>cat triad</scene>
===Mechanism===

== Structural highlights ==

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.

</StructureSection>
== References ==

ref name=”Tournier”>PMID:32269349</ref>

<references/>
==Student Contributors==
*Justin Chavez
*Hayden Vissing
*David Bogle

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:49:58Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='350' frame= 'true' side= 'right' caption='AHB2 Inhibitor 7UHB' scene ='10/1075216/Practice/1'>
==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

<scene name='10/1075216/Practice/2'>Overview Image</scene>

Where do we begin... <ref name="Hunt">DOI: 10.1126/scitranslmed.abn1252</ref>.

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor Let's investigate!]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!<ref name="Hunt">DOI: 10.1126/scitranslmed.abn1252</ref>.]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==

===PDB Files===
[1]https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:47:07Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='350' frame= 'true' side= 'right' caption='AHB2 Inhibitor 7UHB' scene ='10/1075216/Practice/1'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

<scene name='10/1075216/Practice/2'>Overview Image</scene>

Where do we begin... <ref name="Hunt">DOI: 10.1126/scitranslmed.abn1252</ref>.

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor Let's investigate!]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==

===PDB Files===
[1]https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxJustin

2025-03-18T19:39:25Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='6tht' size='350' frame='true' side='right' caption='ICCG PDB:6tht' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxJustin'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Introduction==
*[https://en.wikipedia.org/wiki/Cutinase Cutinase]
==Function==
==3-D Overview==
[[Image:11_res.png|400 px|right|thumb|Figure 1]]
==Active Site==
here is the <scene name='10/1075217/Cat_triad/1'>cat triad</scene>
===Mechanism===

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>
==Student Contributors==
*Justin Chavez
*Hayden Vissing
*David Bogle

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:37:45Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='350' frame= 'true' side= 'right' caption='AHB2 Inhibitor 7UHB' scene ='10/1075216/Practice/1'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

<scene name='10/1075216/Practice/2'>Overview Image</scene>

Where do we begin...

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor Let's investigate!]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:35:13Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='350' frame= 'true' side= 'right' caption='AHB2 Inhibitor 7UHB' scene ='10/1075216/Practice/1'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor Let's investigate!]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:20:49Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='350' frame= 'true' side= 'right' caption='AHB2 Inhibitor 7UHB' scene =' '>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor Let's investigate!]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:18:52Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor Let's investigate!]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxJustin

2025-03-18T19:17:27Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='6tht' size='350' frame='true' side='right' caption='ICCG PDB:6tht' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxJustin'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Introduction==
*[https://en.wikipedia.org/wiki/Cutinase Cutinase]
==Function==
==3-D Overview==
[[Image:11_res.png|400 px|right|thumb|Figure 1]]
==Active Site==
===Mechanism===

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>
==Student Contributors==
*Justin Chavez
*Hayden Vissing
*David Bogle

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:16:07Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:15:42Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? [['Let's investigate!']https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:14:41Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? ['Let's investigate!'https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:14:02Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? ["https://"www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor"]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:13:30Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

Where do we begin...

It all starts at the ACE2 receptor, but what is that? [https://www.asbmb.org/asbmb-today/science/051620/what-is-the-ace2-receptor]

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:09:07Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

[[Image:Spike with Covid.png|400 px|lef|thumb|Figure Legend: The coolest image of this protein EVAH and it was handmade!!!]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:08:21Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

[[Image:Spike with Covid.png|100 px|lef|thumb|Figure Legend: An overview image of the ACE2 receptor]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:06:51Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

[[Image:Spike with Covid.png]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

File:Spike with Covid.png

2025-03-18T19:06:04Z

Mark Macbeth:

User:Mark Macbeth/SandboxGiavanna

2025-03-18T19:04:21Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

[[Image:]]

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth

2025-03-18T19:03:03Z

Mark Macbeth:

* Assistant Professor

* Department of Chemistry and Biochemistry

* Butler University

* Indianapolis, IN, USA

* Areas of Interest: Biochemistry, Structural Biology, RNA•Protein Interaction, Enzyme Catalysis

* Post-doctoral Howard Hughes Medical Institute and University of Utah School of Medicine

* Ph. D. Biochemistry and Molecular Biology, The University of Chicago

* B. S. Biological Sciences, University of Vermont

* [[User:Mark Macbeth/Sandbox1]]

* [[User:Mark Macbeth/Sandbox10]]

* [[User:Mark Macbeth/Sandbox12]]

* [[User:Mark Macbeth/Sandbox13]]

* [[User:Mark Macbeth/Sandbox14]]

* [[User:Mark Macbeth/SandboxCarson]]

* [[User:Mark Macbeth/SandboxJustin]]

* [[User:Mark Macbeth/SandboxGiavanna]]

* [[Histone Modifying Enzymes]]

* [http://proteopedia.org/wiki/index.php/CH462_Butler CH462 Student Authored Pages]

* [http://proteopedia.org/wiki/index.php/Histone_Lysine_Methyltransferase_SET7/9 Histone Lysine Methyltransferase: SET7/9]

* [http://proteopedia.org/wiki/index.php/Histone_deacetylase_8_%28HDAC8%29 Histone deacetylase 8 (HDAC8)]

* [http://proteopedia.org/wiki/index.php/Histone_acetyltransferase_1-2_Complex_%28HAT1/2%29 Histone acetyltransferase 1-2 Complex (HAT1/2)]

* [http://proteopedia.org/wiki/index.php/Lysine-specific_demethylase_1_%28LSD-1%29 Lysine-specific demethylase 1 (LSD-1)]

File:Spike Protein on Covid.png

2025-03-18T19:00:45Z

Mark Macbeth: uploaded a new version of "Image:Spike Protein on Covid.png"

File:Spike Protein on Covid.png

2025-03-18T19:00:34Z

Mark Macbeth:

File:11 res.png

2025-03-18T18:59:16Z

Mark Macbeth:

File:New fogged overview.png

2025-03-18T18:59:10Z

Mark Macbeth: This shows an overview image of the ACE2 receptor.

This shows an overview image of the ACE2 receptor.

User:Mark Macbeth/SandboxJustin

2025-03-18T18:57:33Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxJustin'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Introduction==
==Function==
==3-D Overview==
==Active Site==
===Mechanism===

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>
==Student Contributors==
*Justin Chavez
*Hayden Vissing
*David Bogle

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:57:10Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
https://www.rcsb.org/structure/7UHB

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:56:55Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
<https://www.rcsb.org/structure/7UHB>

==Student Contributors==
*Giavanna Yowell
*Shea Bailey
*Matthew Pereira

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:56:13Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
<https://www.rcsb.org/structure/7UHB>

==Student Contributors==
*Giavanna Yowell*
*Shea Bailey*
*Matthew Pereira*

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:54:49Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==
Covid was a terrible pandemic that required a vaccine and here it is!

==Function==

==Mechanism==

==Active Site==

==Inhibitor Differences==

</StructureSection>

==References==
===PDB Files===
g) <references/https://www.rcsb.org/structure/7UHB> (code to list your actual full references here)
h) ==Student Contributors== (a section for recognition of your team)
*Name of Student
Week 8 – Page 4 of 9
*Name of Student
*Name of Student

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:51:09Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='7UHB' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==

d) All content that you add will come next with appropriate subheaders for different sections
of your page (i.e ==Function== and ==Mechanism== on your generic page), with further
subheadings like ===Active Site=== or ===Extracellular Domain=== (note the 3 ‘=’ signs)
e) </StructureSection> (This code ends the main content that you will have added)
f) ==References== (A heading section for the articles you reference)
g) <references/> (code to list your actual full references here)
h) ==Student Contributors== (a section for recognition of your team)
*Name of Student
Week 8 – Page 4 of 9
*Name of Student
*Name of Student

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:50:43Z

Mark Macbeth:

=SARS CoV-2 Protein Inhibitors (AHB2 and LCB1/LCB3)=

<StructureSection load='AHB2' size='340' side='right' caption='AHB2 Inhibitor'>

==Introduction==

d) All content that you add will come next with appropriate subheaders for different sections
of your page (i.e ==Function== and ==Mechanism== on your generic page), with further
subheadings like ===Active Site=== or ===Extracellular Domain=== (note the 3 ‘=’ signs)
e) </StructureSection> (This code ends the main content that you will have added)
f) ==References== (A heading section for the articles you reference)
g) <references/> (code to list your actual full references here)
h) ==Student Contributors== (a section for recognition of your team)
*Name of Student
Week 8 – Page 4 of 9
*Name of Student
*Name of Student

User:Mark Macbeth/SandboxJustin

2025-03-18T18:49:24Z

Mark Macbeth:

=''ICCG PET Hydrolase''=

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxJustin'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

=='''Introduction'''==
=='''3-D Overview'''==
===Active Site===
====Mechanism====

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:43:03Z

Mark Macbeth:

=COVID Inhibitors=

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxGiavanna'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:42:18Z

Mark Macbeth:

=COVID Inhibitors=

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxGiavanna'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Practice==

=== Function ===

== Disease ==

== Relevance ==

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:41:24Z

Mark Macbeth:

=COVID Inhibitors=

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxGiavanna'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

==Practice==

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:40:51Z

Mark Macbeth:

=COVID Inhibitors=
==Practice==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxGiavanna'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>

User:Mark Macbeth/SandboxGiavanna

2025-03-18T18:37:53Z

Mark Macbeth:

=COVID Inhibitors=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Mark Macbeth/SandboxGiavanna'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

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.

</StructureSection>
== References ==
<references/>