Sandbox7 Eric Martz

Proposed Title: <span style="font-size:150%">'''Nitrotyrosine.'''</span>

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This page is reserved for a collaboration between [[User:Eric Martz]] and [http://www.cancer.ucla.edu/index.aspx?page=645&recordid=338 Hermes J Garbán].

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[[Image:800px-Nitrotyrosine.png|right|thumb|3-Nitrotyrosine]]

Nitrotyrosine<ref>[[User:Eric Martz]] wishes to thank [http://www.cancer.ucla.edu/index.aspx?page=645&recordid=338 Hermes J. Garbán] for bringing nitrotyrosine to his attention.</ref> results from the post-translational modification of the [[Amino_Acids|standard amino acid]] tyrosine. Reactive nitrogen compounds produced in inflammation are typically responsible. Nitrosylation of tyrosine tends to inactivate enzymes.

In March, 2011, there are 13 entries in the [[PDB]] containing coordinates for 3-nitrotyrosine (meta-nitro-tyrosine), with the [[http://www.proteopedia.org/wiki/index.php/Non-Standard_Residues|compound ID]] '''NIY'''. These include six sequence-distinct proteins, represented by ribonucleotide reductase [[2xof]] and [[2xap]], laccase [[3div]], Human Manganese Superoxide Dismutase [[2adp]], Human Glutathione Reductase [[1k4q]], and bovine Cu,Zn superoxide dismutase [[1sda]]. Not surprisingly, the NO₂ adduct, being very hydrophilic, is often on the surface of the protein.

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<Structure size='450' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here'

scene='Sandbox7_Eric_Martz/Cartoon/1' />

One of the more interesting cases may be Human <font color="#00c000">'''Manganese'''</font> Superoxide Dismutase, for which structures are available for the wild type [[2adq]], shown at right (<scene name='Sandbox7_Eric_Martz/Cartoon/1'>restore initial scene</scene>), and the nitrated form, [[2adp]]. In this structure, <font color="#00c000">'''Mn⁺⁺'''</font> is <scene name='Sandbox7_Eric_Martz/Cartoon/2'>buried</scene>. The is

<scene name='Sandbox7_Eric_Martz/Mn_contacts/1'>caged</scene> by four histidine <font color="#3050F8">'''nitrogens'''</font>, one aspartate <font color="#ff0d0d">'''oxygen'''</font>, and one <font color="magenta">'''water'''</font>. Tyrosine 34 is nearby (5.2 &Aring;ngstroms), but not near enough to be interacting with the <font color="#00c000">'''Mn⁺⁺'''</font> or its cage.

<scene name='Sandbox7_Eric_Martz/Contacts_to_nitrotyrosine/1'>Nitrosylation of tyrosine 34</scene> extends it towards the <font color="#00c000">'''Mn⁺⁺'''</font>. The partially negatively charged <font color="#ff0d0d">'''oxygens'''</font> in the NO₂ are 3.6-3.8 &Aring; from the electron-hungry <font color="#00c000">'''Mn⁺⁺'''</font>. <scene name='Sandbox7_Eric_Martz/Aligned_pre_and_post_nitro/2'>Nitrosylation pushes the tyrosine ring</scene> slightly farther from the <font color="#00c000">'''Mn⁺⁺'''</font>, but causes no other significant conformational changes<ref>[[DeepView]] was used to align all atoms of the three Mn-coordinating histidines. In the resulting file [[Image:2adq-2adp-3hisaln.pdb]], 2adq is model 1, and 2adp is model 2.</ref>. The authors<ref>PMID: 16443160</ref> conclude

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"Inhibition of catalysis can be attributed to a steric effect of 3-nitrotyrosine 34 that impedes substrate access and binding, and alteration of the hydrogen-bond network that supports proton transfer in catalysis. It is also possible that an electrostatic effect of the nitro group has altered the finely tuned redox potential necessary for efficient catalysis, although the redox potential of nitrated MnSOD has not been measured."

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==See Also==

* [http://en.wikipedia.org/wiki/Nitrotyrosine Nitrotyrosine] in Wikipedia.

==Notes==

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