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This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439.

1 Vitamin D activation by cytochrome P450, Rickets (3c6g)^[1]
2 Introduction
3 Quiz Question 1
4 See Also
5 Credits
6 References

Vitamin D activation by cytochrome P450, Rickets (3c6g)^[1]

by Isabel Hand, Elizabeth Humble, Kati Johnson, Samantha Kriksceonaitis, and Matthew Tiller

Student Projects for UMass Chemistry 423 Spring 2016

Introduction

Rickets is a disease resulting from prolonged vitamin D deficiency. As vitamin D is vital for the absorption of phosphorus and calcium, a deficiency would cause weakening of bones. Rickets also causes muscle weakness, skeletal deformities, dental problems, inhibition of growth, and muscle spasms. In some cases, rickets can be inherited due to mutations in genes responsible for coding for human CYP2R1.

In the human body, CYP2R1, a member of the cytochrome P450 family, is responsible for the first steps of the conversion of vitamin D into a bioavailable form within the liver. CYP2R1 is also known as Vitamin D 25-hydroxylase as it hydroxylates vitamin D3 into calcidiol, the bioavailable form of the vitamin, which would then be converted to calcitriol via the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, as seen in figure 1.

Fig. 1, the conversion of vitamin D3 into calcidiol via Vitamin D 25-hydroxylase

is shown with amino acids in teal and the heme center shown as a space filling model, with the nitrogen shown in blue, carbon in gray, oxygen in red, and the iron center shown in orange

Overall Structure

Cytochrome P450 is an , which means the protein is made of two subunits that are structurally very similar to one another, but not identical. Each dimeric subunit contain 12 α-helices (labeled A-L) along with some β-sheets that are localized to one side of the molecule. Helices F and G from each of the units form the dimer interface of cytochrome P450, and are involved in the formation of the active site. This dimeric interface of the protein is stabilized by between residues from the G helix of one the units with residues located on the the F helix of the second unit, and vice versa. Two molecules of 2-hydroxypropyl-β-cyclodextrin are also found near the dimer interface. The cyclodextrins are believed to help further stabilize the protein, and also shield the hydrophobic part of the F-G helix transition loop from the solvent by . Cytochrome P450 has an apparent mass of ~120 kDa.

Binding Interactions

CYP2R1 binds vitamin D3 at an extended binding site that orients the bound molecule to bring its side chain close to the heme and allow for hydroxylation. The binding site is located at the channel between the G and I helices and the B' helix/B-C loop. The active site has non-polar residues which allows for nonpolar interactions with D3. In the you can see the residues that interact to bind Vitamin D3 and the channel between. Once bound, the D3 molecule is submerged into the protein, with only its 3-OH group showing. The B' helix is one of the substrate recognition sites and has a flexible C terminus which unwinds outward to allow entrance of the substrate into the active site channel. Due to the stabilizing interactions of B' with the F-G loop, binding of the substrate causes the protein to adopt a closed conformation which closes the access channel.

Additional Features

Cytochrome P450 has a central iron-bound heme, which, combined with its structural conformation, allows for hydroxylation with the attached substrate. Cytochrome P450 has specific vitamin D 25-hydroxylase activity, which does not function properly when a person has rickets. Rickets is caused by a lack of sufficient vitamin D in their system, which is often caused by a vitamin D-25 hydroxylation defect. Leu99Pro is an evolutionarily conserved mutation in the beta helix which contributes to the hydroxylation defect. Leu99 does not inhibit substrate binding; however, Leu99Pro disturbs hydrogen binding around the heme and interferes with the helix steric properties, causing protein instability. When Leu99 does not have the proline mutation, its carboxyl group forms hydrogen bonds with Arg445, which are both located around the central heme and allows for hydroxylation of vitamin D.

Quiz Question 1

1A) Why is Proline so poorly suited for inclusion in Alpha Helices?

    A) It cannot hydrogen bond due to the position of its amide
    B) The residue is incapable of forming the correct phi and psi angles in a helix
    C) The steric hindrance of its sidechain
    D) A and C
    E) All of the above

1B) This protein being a dimer, has symmetry between its two large sections, from where most of the molecule has been cut away for simplicity, you can see where one half (in green) comes within close proximity of the other half (in blue). These 2 pairs of helices help hold the dimer together via electrostatic interactions. If the black residue is Arg, and the white residue is Asp, what is most likely to be on the opposite helix

       (Arg match, Asp match)
    A) Asp, His
    B) Gly, Val
    C) Met, Lys

Credits

Introduction - Sami Kriksceonaitis

Overall Structure - Kati Johnson

Binding Interactions - Isabel Hand

Additional Features - Elizabeth Humble

Quiz Question 1 - Matthew Tiller

References

↑ Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW. Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol. 2008 Jun 27;380(1):95-106. Epub 2008 Apr 8. PMID:18511070 doi:10.1016/j.jmb.2008.03.065

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+=='''Vitamin D activation by cytochrome P450, Rickets (3c6g)<ref>PMID: 18511070 </ref>'''==
+by Isabel Hand, Elizabeth Humble, Kati Johnson, Samantha Kriksceonaitis, and Matthew Tiller
-='''MTH1/crizotinib'''=
+[[Student Projects for UMass Chemistry 423 Spring 2016]]
 ==Introduction==
-<Structure load='4c9x' size='300' frame='true' align='right' caption='Basic Structure of MTH1/S-crizotinib' scene='48/483888/Basic/1' />
+Rickets is a disease resulting from prolonged vitamin D deficiency. As vitamin D is vital for the absorption of phosphorus and calcium, a deficiency would cause weakening of bones. Rickets also causes muscle weakness, skeletal deformities, dental problems, inhibition of growth, and muscle spasms. In some cases, rickets can be inherited due to mutations in genes responsible for coding for human CYP2R1.
-<br>
+In the human body, CYP2R1, a member of the cytochrome P450 family, is responsible for the first steps of the conversion of vitamin D into a bioavailable form within the liver. CYP2R1 is also known as Vitamin D 25-hydroxylase as it hydroxylates vitamin D3 into calcidiol, the bioavailable form of the vitamin, which would then be converted to calcitriol via the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, as seen in figure 1.
-MTH1 is known as 7,8-dihydro-8-oxuguanine triphosphate (2). MTH1 is a protein in the human body encoded by the NUDT1 gene. In general, MTH1 is often synonymous for the gene NUDT1.The protein belongs to the Nudix hydrolase family, and is characterized by a conserved of 23 – residue sequence segment. MTH1 is part of the Nudix hydrolyse family, it has the typical Nudix structure, fold, <scene name='48/483888/Alpha_beta/1'>alpha/beta/alpha</scene> structure  arranged as a mixed of <scene name='48/483888/Beta_sheet/4'>β- sheet</scene> with one <scene name='48/483888/Alpha_helix/5'>alpha helix</scene> on each side.
+[[Image:Action_Of_CYP2R1.jpg]]
-MTH1 prevents the misincorporation of oxidized nucleotides into DNA. Reactive oxygen species (ROS) produced as byproducts from cellular metabolism can cause damage to DNA and free nucleotides. Misincorporation of oxidized nucleoside triphosphates into DNA and RNA is one cause of mutation during transcription and replication that can result in DNA damage and ultimately cell death. MTH1 performs the hydrolysis of a triphosphate nucleotide to a monophosphate nucleotide to prevent this incorporation. The hydrolysis of the triphosphate nucleotide 8-oxo-dGTP to the monophosphate nucleotide 8-oxo-dGMP will not be recognized by DNA polymerase (1).  This misincorporation of oxidized nucleotides could be used as a tool to combat tumor growth. Cancer cells frequently overexpress MTH1, however; suppressing this protein could cause an increase in DNA misincorporations and induce cell death in tumors.
+Fig. 1, the conversion of vitamin D3 into calcidiol via Vitamin D 25-hydroxylase
-MTH1 is inhibited by <scene name='48/483888/S-crizotinib/2'>(S)-Crizotinib</scene>. Crizotinib has an aminopyridine structure and  functions as a protein kinase inhibitor because it binds with the ATP – binding pocket of target kinase (3). Crizotinib has a high impact in drug design because it causes tumors to shrink and stabilize. It has been shown that when (S)-Crizotinib inhibits MTH1, DNA single–strand breaks are more prevalent and DNA repair in colon carcinoma cells is activated. When (S)-Crizotinib inhibits MTH1, the protein can no longer function as a nucleotide ‘healer’, and the impairment rate of the nucleotide pool is increased. One study showed MTH1 impairs growth of KRAS tumor cells and an overexpression of MTH1 mitigates the cancer cells(4). Targeting MTH1 and other enzymes which control the cleansing of oxidized nucleotides as a tumor-specific strategy may represent a novel strategy for difficult-to-treat tumors.
+<scene name='48/483888/Human_p450/1'>Human P450 Cytochrome</scene> is shown with amino acids in teal and the heme center shown as a space filling model, with the nitrogen shown in blue, carbon in gray, oxygen in red, and the iron center shown in orange
+<StructureSection load='3c6g' size='350' side='right' caption='Structure of Human Cytochrome p450' scene=''>
 ==Overall Structure==
-<Structure load='4c9x' size='300' frame='true' align='right' caption='Basic Structure of MTH1/S-crizotinib 4c9x' scene='48/483888/Basic/1' />
-<br> MTH1/S-crizotinib is a member of a protein family of phosphorohydrolases known as the Nudix family (2). Proteins in the Nudix family are used to hydrolyze nucleoside phosphates; they also act as catalysts for the same reaction. Proteins in the Nudix family consist of two unique parts: <scene name='48/483888/Backbone/1'>a Nudix fold and a Nudix motif</scene> (2). The Nudix fold is the secondary structure, or backbone, of the protein; the backbone has an α/β/α structure, meaning that the backbone consists of mixed beta sheet (gold) with an alpha helix on each end (magenta) (2).
+Cytochrome P450 is an <scene name='48/483888/Cytochrome_p450_dimer/1'>asymmetric dimer</scene>, which means the protein is made of two subunits that are structurally very similar to one another, but not identical. Each dimeric subunit contain 12 α-helices (labeled A-L) along with some β-sheets that are localized to one side of the molecule. Helices F and G from each of the units form the dimer interface of cytochrome P450, and are involved in the formation of the active site. This dimeric interface of the protein is stabilized by <scene name='48/483888/Cytochrome_p450_interface/1'>hydrogen bonding interactions</scene> between residues from the G helix of one the units with residues located on the the F helix of the second unit, and vice versa. Two molecules of 2-hydroxypropyl-β-cyclodextrin are also found near the dimer interface. The cyclodextrins are believed to help further stabilize the protein, and also shield the hydrophobic part of the F-G helix transition loop from the solvent by <scene name='48/483888/Cytochrome_p450_cyclodextrins/1'>encapsulating the Phe240 residue within its cavity</scene>. Cytochrome P450 has an apparent mass of ~120 kDa.
-	The second component of proteins in the Nudix family, such as MTH1/S-crizotinib, is the Nudix motif, which is different for every protein. The Nudix motif in MTH1/S-crizotinib is made up of 23 amino acid sequence that orient into a small alpha helix (dark purple) (5,6). This helix attached to one of the main alpha helices in MTH1/S-crizotinib’s backbone. The amino acids that catalyze the hydrolysis reactions are located in this alpha helix (2,5,6). All of these components establish the <scene name='48/483888/Polarity/1'>polarity</scene> of the protein; the outer parts of the helices and beta sheet are polar and hydrophilic (purple), while the inner parts and non polar and hydrophobic (gray).
-	MTH1/S-crizotinib also has an <scene name='48/483888/Active_site_of_mth1/2'>active site pocket</scene> that is formed between the beta sheet and one of the alpha helices (2). This pocket is built out of the residues Leu9 (aqua), Phe27 (violet), Phe72 (magenta), Met81 (lime green), Val83 (brown), Trp117 (orange), Trp123 (gold), and Phe139 (salmon). Furthermore, the amino acid <scene name='48/483888/4c9x-_the_glu_100_amino_acid/2'>Glu100</scene> (magenta) is used to coordinate metal-binding in the protein and is located outside the alpha helix motif (2).
-	MTH1/S-crizotinib has three different types of ligands attached to it: one chloride ligand, five sulfate ligands, and the <scene name='48/483888/S-crizotinib_ligand/2'>S-crizotinib ligand</scene>. Crizotinib is a tyrosine kinase inhibitor, and its molecular structure is C21H22Cl2FN5O. The stereochemistry of the crizotinib determines if this inhibitor prevents MTH1 from carrying out its purpose in cancer cells; the S-crizotinib stops MTH1 from working while the R-crizotinib has no effect on the protein (3,7).
-<br>
-<br><br><br><br><br><br>
 ==Binding Interactions==
-<Structure load='4c9x' size='300' frame='true' align='right' caption='4c9x, (S)-crizotinib in MTH1 Binding Pocket' scene='48/483888/Binding_interactions/3' />
-<br>
+CYP2R1 binds vitamin D3 at an extended binding site that orients the bound molecule to bring its side chain close to the heme and allow for hydroxylation. The binding site is located at the channel between the G and I helices and the B' helix/B-C loop. The active site has non-polar residues which allows for nonpolar interactions with D3. In the <scene name='48/483888/Spacefilled_binding_site/1'>space filling representation </scene> you can see the residues that interact to bind Vitamin D3 and the channel between. Once bound, the D3 molecule is submerged into the protein, with only its 3-OH group showing.
-Human MutT homologue, also known as MTH1, is a nucleotide pool sanitization enzyme and the target for crizotinib, a competitive inhibitor. Crizotinib is a kinase inhibitor that suppresses MTH1 activity in concentrations as low as nanomoles/liter, suggesting high levels of specificity (1). Crizotinib acts on MTH1 through competitive inhibition, meaning it displaces kinases, the usual substrates. Because the specificity of the binding pocket of MTH1 depends on the stabilization of the enol tautomer of 8-oxo-dGTP, crizotinib’s chemistry interacts with this conformation to be effective (2). The binding of crizotinib yields no major structural changes in the MTH1 protein.
+The B' helix is one of the substrate recognition sites and has a flexible C terminus which unwinds outward to allow entrance of the substrate into the active site channel. Due to the stabilizing interactions of B' with the F-G loop, binding of the substrate causes the protein to adopt a closed conformation which closes the access channel.
-The most significant interactions between crizotinib and the MTH1 active site are hydrogen bonding interactions. Hydrogen bonding occurs between the Asparagine residue 33 and the N3 of 8-oxo-dGMP and between the acidic Aspartate residues 119 and 120 and the oxygen in 8-oxo-dGMP. Both the Asp 119 residue and the Asn 33 residue are crucial to binding specificity (2). Because crizotinib has a chiral center, the (S) and (R) enantiomers act differently in the binding pocket of MTH1. After recent testing of MTH1 using both enantiomers, the (S) enantiomer has shown a higher affinity for the MTH1 binding pocket, whereas the (R) enantiomer is a better inhibitor for most other similar protein kinases. An eclipsed conformation of a methyl group at the chiral center and a chlorine attached to the benzyl ring are responsible for reducing the energetic favorability of the (R) enantiomer in the binding pocket of MTH1 (1).
-<br><br><br><br><br><br><br><br>
 ==Additional Features==
-<Structure load='4c9x' size='300' frame='true' align='right' caption='4c9x, Hydrophillic and Hydrophobic Residues' scene='48/483888/Hydrophilic_and_hydrophopic/1'/>
-The <scene name='48/483888/Acidic_basic_residues/3'>acidic (red) and basic residues (blue)</scene> can be seen inside the globular protein structure. The majority of the residues appear exposed on the protein surface rather than buried within the protein. Acidic and basic residues are also prevalent within the binding pocket.
-MTH1 structurally recognizes and distinguishes 8-oxo-dGTP from 8-oxo-dGMP different from one another. In order to understand how MTH1 functions, this is essential to explore. The protein MTH1 has been co-crystallized with the substrate 8-oxo-dGTP and the structure of the crystal was observed (2). A reaction took place and the product, 8-oxo-dGMP, was bound in a pocket formed by the <scene name='48/483888/Alpha_helix_2_beta_sheet/1'>beta sheet and helix 2</scene>. This green scene representation is not exact, and a structural change may have occurred upon 8-oxo-dGTP binding. <scene name='48/483888/Asp_120_asn_33/1'>Asn 33 and ASP 120</scene> make hydrogen bonds to the 2-amino group of 8-oxo-dGMP. This amino position is central for the interaction. Nucleotide analogs were used to test MTH1 substrate recognition; results were in agreement. Removal of the 2-amino group led to a 10-fold less effective degradation (2). Mg<sup>2+</sup> also appeared in the co-crystal structure, but the electron density, coordination geometry, and coordination distances showed Mg<sup>2+</sup> was not bound to the complex. It was hypothesized that Mg<sup>2+</sup> may coordinate with the substrate of the triphosphate nucleotide (2). Many other residues involved in specificity and recognition have been identified.
+Cytochrome P450 has a central iron-bound heme, which, combined with its structural conformation, allows for hydroxylation with the attached substrate.  Cytochrome P450 has specific vitamin D 25-hydroxylase activity, which does not function properly when a person has rickets.  Rickets is caused by a lack of sufficient vitamin D in their system, which is often caused by a vitamin D-25 hydroxylation defect.  Leu99Pro is an evolutionarily conserved mutation in the beta helix which contributes to the hydroxylation defect.  Leu99 does not inhibit substrate binding; however, Leu99Pro disturbs hydrogen binding around the heme and interferes with the helix steric properties, causing protein instability.   When Leu99 does not have the proline mutation, its carboxyl group forms hydrogen bonds with Arg445, which are both located around the central heme and allows for hydroxylation of vitamin D.
-[[Image:Resize of MTH1reactionsedit.jpg|thumb|400px|center|'''8-oxo-dGTP to 8-oxo-dGMP '''                                <br> Modified from: http://aci.cm.umk.pl/~karolb/activity.htm]]
-MutT is a homolog of MTH1, shares the same nubix family, and is expressed in ''Escherichia coli''. MutT also catalyzes the hydrolysis of 8-oxo-dGTP to 8-oxo-dGMP, but has a 21% (low) sequence identity to MTH1. Co-crystal structure produced the ''anti'' conformation of bound 8-oxo-dGMP in MTH1 while ''syn'' conformation was observed in MutT (2). From the crystal structure it was determined that the base–protein interactions are quite different and reveal no conservation of structure. Although the proteins shared a conserved catalytic region, the nucleotide recognition was not conserved. Diverging evolutionary routes have been taken, and one possibility is to allow MTH1 to evolve more non-specific substrate specificity (2). Understanding the mechanisms of non-specific substrate binding could be an important step to developing new inhibitors for similar enzymes.
+<scene name='48/483888/Hemegroup/1'>Leu99 and Arg445</scene>
+</StructureSection>
 ==Quiz Question 1==
-<Structure load='4c9w' size='300' frame='true' align='right' caption='MTH1 protein structure' scene='48/483888/Rainbow_cartoon_1/1' />
+A) Why is Proline so poorly suited for inclusion in Alpha Helices?
+     A) It cannot hydrogen bond due to the position of its amide
+     B) The residue is incapable of forming the correct phi and psi angles in a helix
+     C) The steric hindrance of its sidechain
+     D) A and C
+     E) All of the above
-<scene name='48/483888/Rainbow_cartoon_1/1'>Rainbow Cartoon Model</scene> - This scene colors the protein from the N-terminus to the C terminus.
+B) This protein being a dimer, has symmetry between its two large sections, from <scene name='48/483888/Gandfhelices/1'>this orientation</scene> where most of the molecule has been cut away for simplicity, you can see where one half (in green) comes within close proximity of the other half (in blue).  These 2 pairs of helices help hold the dimer together via electrostatic interactions.  If the black residue is Arg, and the white residue is Asp, what is most likely to be on the opposite helix
+        (Arg match, Asp match)
-<scene name='48/483888/Mjt_backbone_as/1'>Active Site Residues Model</scene> - This scene shows the active site of the protein. Individual amino acids are labelled and active site residues are colored according to charge (red = positive, blue = negative, white = uncharged). The ligand (S-crizotinib) in the center is colored by atom (Black = Carbon, Red = Oxygen, Blue = Nitrogen, Green = Halogen).
+     A) Asp, His
+     B) Gly, Val
-<br>
+     C) Met, Lys
-'''Using the green scenes provided above, answer the following:'''<br>
-a.) Suppose there is a point mutation causing a change at ASP-120 in MTH1. Which of the following amino acids substitutions would be '''least''' likely to affect substrate binding? Explain your reasoning.
-<blockquote>1.) Lysine (LYS)<br>2.) Glutamate (GLU)<br>3.) Glycine (GLY)</blockquote>
-b.) If there were a point mutation at PHE-27, which of the following amino acid substitutions would likely affect ligand binding the '''most'''? Again, explain your reasoning.
-<blockquote>1.) Tryptophan (TRP)<br>2.) Tyrosine (TYR)<br>3.) Arginine (ARG)</blockquote>
-<br><br>
-==Quiz Question 2==
-<br>
-The above two green scenes highlight the chiral center of the MTH1 inhibitor called crizotinib. Research has shown that the (S)-enantiomer binds with more affinity to it's MTH1 substrate but that it is not due to interaction with the protein itself at the binding site.
-<Structure load='4c9x' size='300' frame='true' align='left' caption='(S)-Enantiomer of Inhibitor at Binding Site' scene='48/483888/S-enantiomer_zoom_in/4'/>
-<Structure load='4c9x' size='300' frame='true' align='center' caption='(R)-Enantiomer of Inhibitor at Binding Site' scene='48/483888/R-enantiomer_zoomed_in/1'/>
-<br><br>
-[[Image:S-crizo.gif|300px|left|thumb| Crizotinib Structure Modified from adooq.com]]
-<br><br>
-Using the green scenes and the structure image can you see an unfavorable interaction near the chiral center in the (R)-enantiomer that does not exist in the (S)-enantiomer? Explain.
-<br><br>
-The conformation of the enantiomer is ___________ unfavored.
-<br><br>
-<br><br><br><br><br><br><br>
 ==See Also==
-* [[MTH1]] (7,8-dihydro-8-oxoguanine triphosphatase)
+*[[Cytochrome P450]]
-<br>
+*[[Drug Metabolism by CYP450 Enzymes]]
+*[[3w0y]]
+*[[3w0c]]
 ==Credits==
-: Introduction - Megi Marina
+Introduction - Sami Kriksceonaitis
-: Overall Structure - Cassandra Martin
-: Drug Binding Site - Ben Ryter
+Overall Structure - Kati Johnson
-: Additional Features - Eric Rice
+Binding Interactions - Isabel Hand
-: Quiz Question 1 - Matt Tuttle
+Additional Features - Elizabeth Humble
-: Quiz Question 2 - Colin Hannahan
+Quiz Question 1 - Matthew Tiller
 ==References==
-# Huber, Kilian V. M., Eidarus Salah, Branka Radic, Manuela Gridling, Jonathan M. Elkins, Alexey Stukalov, Ann-Sofie Jemth, Camilla Göktürk, Kumar Sanjiv, Kia Strömberg, Therese Pham, Ulrika Warpman Berglund, Jacques Colinge, Keiryn L. Bennett, Joanna I. Loizou, Thomas Helleday, Stefan Knapp, and Giulio Superti-Furga. "Stereospecific Targeting of MTH1 by (S)-crizotinib as an Anticancer Strategy." Nature 508 (2014): 222-27. Web.
-# Svensson, Linda M., Ann-Sofie Jemth, Mathhieu Desroses, Olga Loseva, Thomas Helleday, Martin Higbom, and Pal Stenmark. "Crystal Structure of Human MTH1 and the 8-oxo-dGMP Product Complex." Http://www.sciencedirect.com. N.p., 19 Aug. 2011. Web.
-# "Crizotinib | C21H22Cl2FN5O - PubChem." Crizotinib | C21H22Cl2FN5O - PubChem. N.p., n.d. Web. 03 Apr. 2015.
-# Fricker, Janet. "Two Studies Show MTH1 Offers Promising New Target for Cancer Treatment." . Ecancer. Cancer Intelligence, 02 Apr. 2014. Web. 03 Apr. 2015.
-#M. Mishima,; Y. Sakai,; N. Itoh,; H. Kamiya,; M. Furuichi,; M. Takahashi, Y. Yamagata, S. Iwai,; Y. Nakabeppu,; and M. Shirakawa. “Structure of the Human MTH1, a Nudix Family Hydrolase that Selectively Degrades Oxidized Purine Nucleoside Triphosphates”, ''J Biol Chem., 279, no. 32,'' 33806-33815, '''2004'''.
-#S.B. Gabelli,; M.A. Bianchet,; M.J. Bessman,; L.M. Amzel “The structure of ADP-ribose pyrophosphates reveals the structural basis for the versatility of the Nudix family”, ''Nat Struct Biol, 8,'' 467-472,''' 2001'''.
-# "Crizotinib, (S)-." (S)-Crizotinib. N.p., n.d. Web. 03 Apr. 2015.
 <references/>

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Contents

Vitamin D activation by cytochrome P450, Rickets (3c6g)^[1]

Introduction

Overall Structure

Binding Interactions

Additional Features

Quiz Question 1

See Also

Credits

References

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Sandbox Reserved 431

From Proteopedia

Current revision

Contents

Vitamin D activation by cytochrome P450, Rickets (3c6g)[1]

Introduction

Overall Structure

Binding Interactions

Additional Features

Quiz Question 1

See Also

Credits

References

Views

Personal tools

Navigation

Search

Toolbox

Vitamin D activation by cytochrome P450, Rickets (3c6g)^[1]