Sandbox Reserved 1057: Difference between revisions
Perry Rabin (talk | contribs) No edit summary |
No edit summary |
||
| (11 intermediate revisions by 2 users not shown) | |||
| Line 1: | Line 1: | ||
=Dimethylarginine Dimethylaminohydrolase= | |||
<StructureSection load='2CI3' size='340' side='right' caption='Dimethylarginine Dimethylaminohydrolase' scene='75/752351/Ddah/1'> | |||
<StructureSection load=' | |||
== Structure == | ==Introduction== | ||
<scene name='75/752351/Ddah/2'>Dimethylarginine Dimethylaminohydrolase</scene> <span class="plainlinks">[http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/5/3/18.html EC 3.5.3.18]</span> (commonly known as DDAH) is a member of the <span class="plainlinks">[https://en.wikipedia.org/wiki/Hydrolase hydrolase]</span> family of enzymes which use water to break down molecules <ref name="palm">Palm F, Onozato ML, Luo Z, Wilcox CS. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. American Journal of Physiology. 2007 Dec 1;293(6):3227-3245. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/17933965 17933965]</span> doi:<span class="plainlinks">[http://ajpheart.physiology.org/content/293/6/H3227 10.1152/ajpheart.00998.2007]</span></ref>. Additionally, DDAH is a <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide_synthase nitric oxide synthase (NOS)]</span> regulator. It metabolizes free arginine derivatives, namely <span class="plainlinks">[https://en.wikipedia.org/wiki/Asymmetric_dimethylarginine N<sup>Ѡ</sup>,N<sup>Ѡ</sup>-dimethyl-L-arginine (ADMA)]</span> and <span class="plainlinks">[https://en.wikipedia.org/wiki/Methylarginine N<sup>Ѡ</sup>-methyl-L-arginine (MMA)]</span>, which competitively inhibit NOS <ref name="tran">Tran CTL, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway. Atherosclerosis Supplements. 2003 Dec;4(4):33-40. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/14664901 14664901]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S1567568803000321 10.1016/S1567-5688(03)00032-1]</span></ref>. DDAH converts MMA or ADMA to two products: <span class="plainlinks">[https://en.wikipedia.org/wiki/Citrulline L-citrulline]</span> and an amine <ref name="frey">Frey D, Braun O, Briand C, Vasak M, Grutter MG. Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: a basis for the design of specific inhibitors. Structure. 2006 May;14(5):901-911. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/16698551]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S0969212606001717 10.1016/j.str.2006.03.006]</span></ref> (Figure 1). DDAH is expressed in the cytosol of cells in humans, mice, rats, sheep, cattle, and bacteria <ref name="palm" />. DDAH activity has been localized mainly to the brain, kidneys, pancreas, and liver in these organisms. Presented in this page is information from DDAH isoform 1 (DDAH-1); however, there are two different isoforms <ref name="frey" />. | |||
[[Image:DDAH mechanism.jpg|500 px|center|thumb|'''Figure 1.''' The normal DDAH mechanism]] | |||
[[ | ==Different Isoforms== | ||
DDAH has two main isoforms <ref name="frey" />. DDAH-1 colocalizes with <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide_synthase nNOS (neuronal NOS)]</span>. This enzyme is found mainly in the brain and kidneys of organisms <ref name="tran" />. DDAH-2 is found in tissues with <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide_synthase eNOS (endothelial NOS)]</span> <ref name="frey" />. DDAH-2 localization has been found in the heart, kidney, and placenta <ref name="tran" />. Additionally, studies show that DDAH-2 is expressed in iNOS containing immune tissues <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide_synthase (inducible NOS)]</span> <ref name="frey" />. Both of the isoforms have conserved residues that are involved in the catalytic mechanism of DDAH (Cys, Asp, and His). The differences between the isoforms is in the substrate binding residues and the lid region residues. DDAH-1 has a positively charged lid region while DDAH-2 has a negatively charged lid. In total, three salt bridge differ between DDAH-1 and DDAH-2 isoforms <ref name="frey" />. | |||
<ref name=" | ==General Structure== | ||
DDAH-1’s <scene name='69/694225/Secondary_structure_colored/3'>secondary structure</scene> has a <scene name='69/694225/Prop_domains/2'>propeller-like fold</scene> which is characteristic of the superfamily of <span class="plainlinks">[https://en.wikipedia.org/wiki/Arginine:glycine_amidinotransferase L-arginine/glycine amidinotransferases]</span> <ref name="humm">Humm A, Fritsche E, Mann K, Göhl M, Huber R. Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue. Biochemical Journal. 1997 March 15;322(3):771-776. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1218254/ 9148748]</span> doi:<span class="plainlinks">[http://www.biochemj.org/content/322/3/771 10.1042/bj3220771]</span></ref>. This five-stranded <span class="plainlinks">[https://en.wikipedia.org/wiki/Beta-propeller propeller]</span> contains five repeats of a ββαβ motif <ref name="frey" />. These motifs in DDAH form a <scene name='75/752351/Ddah_water_pore/12'>channel</scene> filled with water molecules (red spheres). Lys174 and Glu77 form a <scene name='75/752351/Ddah_salt_bridge/5'>salt bridge</scene> in the channel that makes up the bottom of the <scene name='75/752351/Ddah_active_site/3'>active site</scene>, shown here filled with water molecules. One side of the channel is a <scene name='75/752351/Ddah_water_pore/13'>water-filled pore</scene>, whereas the other side is the active site cleft <ref name="frey" />. | |||
<ref name=" | ===Lid Region=== | ||
Amino acids 25-36 of DDAH constitute the flexible | |||
<scene name='75/752351/Lid_focus/2'>loop region</scene> of the protein, which is more commonly known as the lid region <ref name="frey" />. Studies have shown crystal structures of the lid at <scene name='69/694225/Open_surface/8'>open</scene> and <scene name='69/694225/Closed_surface/5'>closed</scene> conformations. In the open conformation, the lid forms an <scene name='69/694225/Lid_helix/2'>alpha helix</scene> and the amino acid Leu29 is moved so it does not interact with the active site, thus allowing the active site to be vulnerable to attack. When the lid is closed, a <scene name='75/752351/Hbond_leu29/3'>hydrogen bond</scene> can form between the Leu29 carbonyl and the amino group on a bound molecule. This hydrogen bond stabilizes the substrate in the active site. The Leu29 is then <scene name='75/752351/Hbond_leu29/5'>blocking</scene> the active site entrance <ref name="frey" />. Opening and closing the lid takes place faster than the actual reaction in the active site <ref name="rasheed">Rasheed M, Richter C, Chisty LT, Kirkpatrick J, Blackledge M, Webb MR, Driscoll PC. Ligand-dependent dynamics of the active site lid in bacterial Dimethyarginine Dimethylaminohydrolase. Biochemistry. 2014 Feb 18;53:1092-1104. PMCID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945819/ PMC3945819]</span> doi:<span class="plainlinks">[http://pubs.acs.org/doi/abs/10.1021/bi4015924 10.1021/bi4015924]</span></ref>. This suggests that the <span class="plainlinks">[https://en.wikipedia.org/wiki/Rate-determining_step rate-limiting step]</span> of this reaction is not the lid movement, but is the actual chemistry happening to the substrate in the active site of DDAH <ref name="rasheed" />. | |||
The | ====Lid Region Conservation==== | ||
The specific residues in the lid region vary between organisms <ref name="frey" /> (Figure 2). Notable in this image is a <span class="plainlinks">[https://en.wikipedia.org/wiki/Conserved_sequence conserved]</span> leucine <scene name='75/752351/Hbond_leu29/9'>(Leu29)</scene> residue in this led that functions to hydrogen bond with the <span class="plainlinks">[https://en.wikipedia.org/wiki/Ligand ligand]</span> bound to the active site in DDAH-1 but not in DDAH-2 <ref name="rasheed" /> (Figure 2). Different <span class="plainlinks">[https://en.wikipedia.org/wiki/Protein_isoform isoforms]</span> from the same species can have differences in lid regions as well <ref name="frey" />. DDAH-2 has a negatively charged lid while DDAH-1 has a positively charged lid <ref name="frey" />. | |||
[[Image:WebLogo for Lid Region.png|500 px|center|thumb|'''Figure 2.''' WebLogo for the lid region in DDAH-1 of eleven different organisms.]] | |||
The | ===Active Site=== | ||
The normal DDAH regulation <span class="plainlinks">[https://en.wikipedia.org/wiki/Reaction_mechanism mechanism]</span> depends on the presence of <scene name='75/752351/Ddah_active_site/4'>Cys249</scene> in the active site that acts as a <span class="plainlinks">[https://en.wikipedia.org/wiki/Nucleophile nucleophile]</span> in the mechanism <ref name="stone">Stone EM, Costello AL, Tierney DL, Fast W. Substrate-assisted cysteine deprotonation in the mechanism of Dimethylargininase (DDAH) from Pseudomonas aeruginosa. Biochemistry. 2006 May 2;45(17):5618-5630. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/16634643 16634643]</span> doi:<span class="plainlinks">[http://pubs.acs.org/doi/abs/10.1021/bi052595m 10.1021/bi052595m]</span></ref> (Figure 3). The Cys249 is used to attack the <span class="plainlinks">[https://en.wikipedia.org/wiki/Guanidine guanidinium]</span> carbon on the substrate that is held in the active site via <scene name='75/752351/Hbond_leu29/6'>hydrogen bonds</scene>. This is followed by collapsing the tetrahedral product to get rid of the <span class="plainlinks">[https://en.wikipedia.org/wiki/Alkylamines alkylamine]</span> leaving group. A <span class="plainlinks">[https://en.wikipedia.org/wiki/Isothiouronium thiouronium]</span> intermediate is then formed with <span class="plainlinks">[https://en.wikipedia.org/wiki/Orbital_hybridisation sp<sup>2</sup> hybridization]</span>. This intermediate is hydrolyzed to form L-citrulline. The <scene name='75/752351/Ddah_active_site_his162/2'>His162</scene> protonates the leaving group in this reaction and generates hydroxide to hydrolyze the intermediate formed in the reaction (Figure 3). L-citrulline leaves the active site when the lid opens. The amines can either leave through the entrance to the active site or through the <scene name='75/752351/Ddah_water_pore/13'>water-filled pore</scene> <ref name="frey" />. Studies suggest that Cys249 is neutral until binding of guanidinium near Cys249 decreases Cys249’s <span class="plainlinks">[https://en.wikipedia.org/wiki/Acid_dissociation_constant pKa]</span> and deprotonates the thiolate to activate the nucleophile <ref name="stone" />. Other studies suggest that the Cys249 and an active site His162 form an <span class="plainlinks">[https://en.wikipedia.org/wiki/Intimate_ion_pair ion pair]</span> to deprotonate the thiolate. Cys249 and His162 can also form a binding site for inhibitors to bind to which stabilizes the thiolate. This is important in regulating NO activity in organisms and designing drugs to inhibit this enzyme <ref name="stone" />. | |||
[[Image:The Normal DDAH Mechanism.jpg|800px|center|thumb|'''Figure 3.''' The normal mechanism of DDAH highlighting important residues involved.]] | |||
====Channel with Salt Bridge and Water Pore==== | |||
<scene name=' | There is a channel in the center of the protein that is closed by a <scene name='75/752351/Ddah_salt_bridge/6'>salt bridge</scene> connecting Glu77 and Lys174 <ref name="frey" />. This salt bridge constitutes the bottom of the active site. There is a pore containing water on one side of the channel. This pore is <scene name='75/752351/Ddah_water_pore/14'>delineated</scene> by the first β strand of each of the five propeller blades. The water in the channel forms hydrogen bonds to <scene name='75/752351/Ddah_water_pore/15'>His172 and Ser175</scene>. | ||
====Active Site Conservation==== | |||
Active sites of DDAH from different organisms are similar. Amino acids involved in the chemical mechanism of creating products are also <scene name='69/694225/Evolutionary_conservation/3'>conserved</scene> (Figure 4). | |||
[[Image:ColorKey ConSurf NoYellow NoGray.gif|400px|right|thumb|'''Figure 4.''' Color key for DDAH conservation]] | |||
====Zn(II) Bound to the Active Site==== | |||
<span class="plainlinks">[https://en.wikipedia.org/wiki/Zinc Zinc (Zn(II))]</span> acts as an <span class="plainlinks">[https://en.wikipedia.org/wiki/Endogeny_(biology) endogenous]</span> inhibitor of DDAH <ref name="frey" /> (Figure 5). The Zn(II)-binding site is located inside the protein’s active site, making it a <span class="plainlinks">[https://en.wikipedia.org/wiki/Competitive_inhibition competitive inhibitor]</span>. When bound, Zn(II) <scene name='69/694225/Closed_lid_zn9/6'>blocks the entrance</scene> of any other substrate. When <span class="plainlinks">[https://en.wikipedia.org/wiki/Crystallization crystallized]</span> with Zn(II) at <scene name='69/694225/Active_site6/2'>pH 6.3</scene>, an open conformation of the lid region has been shown; however, when Zn(II) is bound at <scene name='69/694225/Active_site_9/3'>pH 9.0</scene>, a closed lid has been observed (Figure 5). | |||
[[Image:Zn(II) bound at differing pH values.jpg|500 px|center|thumb|'''Figure 5.''' Zn(II) bound to the active site of DDAH at differing pH values. A) Zn(II) bound at pH 9.0 showing the channel of DDAH. B) Zn(II) bound at 9.0 showing the closed conformation lid with Leu29 blocking the active site. C) Zn(II) bound at pH 6.3 showing the channel of DDAH. D) Zn(II) bound at pH 6.3 showing the open lid conformation with Leu29 away from the active site.]] | |||
== | =====Important residues in Zinc Binding===== | ||
<scene name='69/ | It was found that Cys273, His172, Glu77, Asp78, and Asp 268 all <scene name='69/694225/Active_site6hbonds/3'>play a role</scene> in the binding of Zn(II). <scene name='69/694225/Cys273_zn/2'>Cys273</scene> directly coordinates with the Zn(II) ion in the active site while the other significant residues stabilize the ion via hydrogen bonding interactions with water molecules in the active site. Depending on pH, His172 can change conformation. At pH 9.0, DDAH-1 has been crystalized with <scene name='69/694225/Active_site_9/2'>His172</scene> in both conformations. Both of these conformations use the <span class="plainlinks">[https://en.wikipedia.org/wiki/Imidazole imidazole]</span> group to directly coordinate the Zn(II) ion. Cys273, which is conserved between bovine and humans, is the key active site residue that coordinates Zn(II) <ref name="frey" />. Zinc-cysteine complexes have been found to be important mediators of protein <span class="plainlinks">[https://en.wikipedia.org/wiki/Catalysis catalysis]</span>, regulation, and structure <ref name="pace">Pace NJ, Weerpana E. Zinc-binding cysteines: diverse functions and structural motifs. Biomolecules. 2014 June;4(2):419-434. PMCID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101490/ 4101490]</span> doi:<span class="plainlinks">[http://www.mdpi.com/2218-273X/4/2/419/htm 10.3390/biom4020419]</span> </ref>. Cys273 and the water molecules stabilize the Zn(II) ion in a tetrahedral environment. The Zn(II) dissociation constant is 4.2 nM which is consistent with the nanomolar concentrations of Zn(II) in the cells, which provides more evidence for the regulatory use of Zn(II) by DDAH <ref name="pace" />. | ||
<scene name='69/ | |||
== | |||
== | ====Inhibitors==== | ||
<scene name='75/752351/Ddah_l-homocysteine/3'>L-homocysteine</scene> and <scene name='75/752351/Ddah_with_l-citrulline/5'>L-citrulline</scene> bind in the active site in the same orientation as MMA and ADMA to create the same <span class="plainlinks">[https://en.wikipedia.org/wiki/Intermolecular_force intermolecular bonds]</span> between them and DDAH <ref name="frey" /> (Figure 6). L-citrulline is also a product of DDAH hydrolyzing ADMA and MMA, suggesting DDAH activity creates a <span class="plainlinks">[https://en.wikipedia.org/wiki/Negative_feedback negative feedback]</span> loop on itself (Figure 3). Both molecules enter the active site and cause DDAH to be in its closed lid formation. The α carbon on either molecule creates three <scene name='75/752351/Hbond_leu29/7'>salt bridges</scene> with DDAH: two with the guanidine group of Arg144 and one with the guanidine group on Arg97. Another salt bridge is formed between the ligand and Asp72. The molecules are stabilized in the active site by <scene name='75/752351/Hbond_leu29/4'>four hydrogen bonds</scene>: α carbon-amino group of the ligand to main chain carbonyls of Val267 and Leu29. Hydrogen bonds also form between the side chains of Asp78 and Glu77 with the ureido group of L-citrulline. | |||
Like L-homocysteine and L-citrulline, <scene name='75/752351/Ddah_s-nitroso-l-homocysteine/4'>S-nitroso-L-homocysteine</scene> binds and the lid region of DDAH is closed (Figure 6). When DDAH reacts with S-nitroso-L-homocysteine, a covalent product, N-thiosulfximide exist in the active site because of its binding to Cys273. N-thiosulfximide is stabilized by several salt bridges and hydrogen bonds. Arg144 and Arg97 stabilize the α carbon-carbonyl group via salt bridges, and Leu29, Val267, and Asp72 stabilize the α carbon-amino group by forming hydrogen bonds <ref name="frey" />. | |||
[[Image:L-citrulline, L-homocysteine, and S-nitroso-L-homocysteine.jpg|500px|center|thumb|'''Figure 6.''' Structures of DDAH inhibitors.]] | |||
==Clinical Relevance== | |||
DDAH works to hydrolyze MMA and ADMA <ref name="frey" />. Both MMA and ADMA competitively inhibit NO synthesis by inhibiting Nitric Oxide Synthase (NOS). NO is made by NOS creating L-citrulline from <span class="plainlinks">[https://en.wikipedia.org/wiki/Arginine L-arginine]</span> <ref name="frey" />. If DDAH is overexpressed, NOS activity will subsequently increase <ref name="frey" />. ADMA and MMA can <span class="plainlinks">[https://en.wikipedia.org/wiki/Enzyme_inhibitor inhibit]</span> the synthesis of NO by competitively inhibiting all three kinds of NOS (endothelial, neuronal, and inducible) <ref name="frey" />. Underexpression or inhibition of DDAH decreases NOS activity and NO levels will decrease. Because of <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide nitric oxide’s (NO)]</span> role in signaling and defense, NO levels in an organism must be regulated to reduce damage to cells <ref name="janssen">Janssen W, Pullamsetti SS, Cooke J, Weissmann N, Guenther A, Schermuly RT. The role of dimethylarginine dimethylaminohydrolase (DDAH) in pulmonary fibrosis. The Journal of Pathology. 2012 Dec 12;229(2):242-249. Epub 2013 Jan. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/23097221 23097221]</span> doi:<span class="plainlinks">[http://onlinelibrary.wiley.com/doi/10.1002/path.4127/references;jsessionid=C34C6C633A21C2ECE14278BBC902AD71.f03t04?globalMessage=0 10.1002/path.4127]</span></ref>. NO is an important signaling and effector molecule in <span class="plainlinks">[https://en.wikipedia.org/wiki/Neurotransmission neurotransmission]</span>, bacterial defense, and regulation of vascular tone <ref name="colasanti">Colasanti M, Suzuki H. The dual personality of NO. ScienceDirect. 2000 Jul 1;21(7):249-252. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/10979862 10979862]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S0165614700014991 10.1016/S0165-6147(00)01499-1]</span></ref>. Because NO is highly toxic, freely diffusible across membranes, and its radical form is fairly reactive, cells must maintain a large control on concentrations by regulating NOS activity and the activity of enzymes such as DDAH that have an indirect effect of the concentration of NO <ref name="rassaf">Rassaf T, Feelisch M, Kelm M. Circulating NO pool: assessment of nitrite and nitroso species in blood and tissues. Free Rad. Biol. Med. 2004 Feb 15;36(4):413-422. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/14975444 14975444]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S0891584903007962 10.1016/j.freeradbiomed.2003.11.011]</span></ref>. An imbalance of NO contributes to several diseases. Low NO levels, potentially caused by low DDAH activity and therefore high MMA and ADMA concentrations, have been associated with diseases such as <span class="plainlinks">[https://en.wikipedia.org/wiki/Uremia uremia]</span>, <span class="plainlinks">[http://www.mayoclinic.org/diseases-conditions/heart-failure/basics/definition/con-20029801 chronic heart failure]</span>, <span class="plainlinks">[https://en.wikipedia.org/wiki/Atherosclerosis atherosclerosis]</span>, and <span class="plainlinks">[https://en.wikipedia.org/wiki/Hyperhomocysteinemia hyperhomocysteinemia]</span> <ref name="tsao">Tsao PS, Cooke JP. Endothelial alterations in hypercholesterolemia: more than simply vasodilator dysfunction. Journal of Cardiovascular Pharmacology. 1998;32(3):48-53. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/9883748 9883748]</span></ref>. High levels of NO have been involved with diseases such as <span class="plainlinks">[https://en.wikipedia.org/wiki/Septic_shock septic shock]</span>, <span class="plainlinks">[http://www.mayoclinic.org/diseases-conditions/migraine-headache/home/ovc-20202432 migraine]</span>, <span class="plainlinks">[https://en.wikipedia.org/wiki/Inflammation inflammation]</span>, and <span class="plainlinks">[https://en.wikipedia.org/wiki/Neurodegeneration neurodegenerative disorders]</span> <ref name="vallance">Vallance P, Leiper J. Blocking NO synthesis: how, where and why? Nat. Rev. Drug Discov. 2002 Dec;1(12):939-950. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/12461516 12461516]</span> doi:<span class="plainlinks">[http://www.nature.com/nrd/journal/v1/n12/full/nrd960.html 10.1038/nrd960]</span></ref>. Because of the effects on NO levels and known inhibitors to DDAH, regulation of DDAH may be an effective way to regulate NO levels, therefore treating these diseases <ref name="frey" />. Additionally, researchers can take advantage of the fact that there are two different isoforms of this enzyme and create drugs that target one isoform over another to control NO levels in specific tissues in the body <ref name="frey" />. | |||
</StructureSection> | |||
__NOTOC__ | |||
== References == | |||
{{reflist}} | |||
== | == Student Contributors == | ||
*Natalie Van Ochten | |||
*Kaitlyn Enderle | |||
*Colton Junod | |||
== 3D Structures of Dimethylarginine Dimethylaminohydrolase == | |||
<span class="plainlinks">[http://proteopedia.org/wiki/index.php/2c6z 2C6Z]</span> L-citrulline bound to isoform 1 | |||
</ | <span class="plainlinks">[http://proteopedia.org/wiki/index.php/2ci1 2CI1]</span> S-nitroso-L-homocysteine bound to isoform 1 | ||
== | |||
< | <span class="plainlinks">[http://proteopedia.org/wiki/index.php/2ci3 2CI3]</span> crystal form 1 | ||
<span class="plainlinks">[http://proteopedia.org/wiki/index.php/2ci4 2CI4]</span> crystal form 2 | |||
<span class="plainlinks">[http://proteopedia.org/wiki/index.php/2ci5 2CI5]</span> L-homocysteine bound to isoform 1 | |||
<span class="plainlinks">[http://proteopedia.org/wiki/index.php/2ci6 2CI6]</span> Zn (II) bound at low pH to isoform 1 | |||
<span class="plainlinks">[http://proteopedia.org/wiki/index.php/2ci7 2CI7]</span> Zn (II) bound at high pH to isoform 1 | |||