Proteopedia - User contributions [en]

User:Abbas Raza/Sandbox 1

2014-04-28T12:33:08Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. There is also a separate proteopedia page on Nei/fpg family [[http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family]].

Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to α/β[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>α-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>β-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> β-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> β-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> β-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>β-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>β-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>β-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>β-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>α-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>α-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>α-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>α-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>α-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>β-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>β-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>α-C and α-D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between β strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif but they were not available in the truncated [[3w0f]] model. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>Arg272, Tyr250 C247, Phe233,Ile194 and Met99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}

=== NEIL1 ===

[[1tdh]], [[3a42]], [[3a45]], [[3a46]], [[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t]], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G (Figure2). [[Image:Dna_lesions.png|thumb|left|300px|'''Figure 2. DNA damages repaired by NEIL3''']]. The reason being that α-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately '''single stranded lesions''' by MmNEIL3 (Figure3)[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 3. Alignment of the alpha-B-alpha-C helices from different NEIL enzymes.''' Analysis of the α-B-α-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145) confirms why 8-oxo-G cannot be recognized easily]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T12:23:52Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. There is also a separate proteopedia page on Nei/fpg family [[http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family]].

Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}

=== NEIL1 ===

[[1tdh]], [[3a42]], [[3a45]], [[3a46]], [[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t]], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G (Figure2). [[Image:Dna_lesions.png|thumb|left|300px|'''Figure 2. DNA damages repaired by NEIL3''']]. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3 (Figure3)[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 3. Alignment of the alpha-B-alpha-C helices from different NEIL enzymes.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145) confirms why 8-oxo-G cannot be recognized easily]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T12:04:18Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. There is also a separate proteopedia page on Nei/fpg family [[http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family]].

Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}

=== NEIL1 ===

[[1tdh]], [[3a42]], [[3a45]], [[3a46]], [[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t]], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C helices from different NEIL enzymes.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145) confirms why 8-oxo-G cannot be recognized easily]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T11:58:48Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. There is also a separate proteopedia page on Nei/fpg family [[http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family]].

Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==

=== NEIL1 ===

[[1tdh]], [[3a42]], [[3a45]], [[3a46]], [[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t]], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C helices from different NEIL enzymes.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145) confirms why 8-oxo-G cannot be recognized easily]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T11:54:39Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. There is also a separate proteopedia page on Nei/fpg family [[http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family]].

Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==

=== NEIL1 ===

[[1tdh]] [[3a42]],[[3a45]], [[3a46]], [[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t]], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T11:47:42Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==

=== NEIL1 ===

[[1tdh]] [[3a42]],[[3a45]], [[3a46]], [[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t]], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T11:45:24Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==

=== NEIL1 ===

[[1tdh]] [[3a42]],[[3a45]], [[3a46]], [[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T11:44:15Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==

=== NEIL1 ===

[[1tdh]] [[3a42]],[[3a45]], [[3a46]],[[3vk7]], [[3vk8]], [[4nrv]], [[4nrw]]

=== NEIL2 ===

[[4mb7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l1t], [[1l2d]], [[1r2z]], [[1pm5]], [[1nnj]], [[1kfv]], [[1pji]], [[3c58]], [[3vk5]], [[2xzu]], [[2xzf]], [[1tdz]], [[1xc8]]

=== Nei ===

[[2eao]], [[2opf]], [[2oq4]], [[1q3c]], [[1q3b]], [[1q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-28T11:39:33Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

=='''3D structures of other Fpg/nei members'''==

=== NEIL1 ===

[[1tdh]] [[3a42]],[[3A45]], [[3A46]],[[3VK7]], [[3VK8]], [[4NRV]], [[4NRW]]

=== NEIL2 ===

[[4MB7]]

=== Fpg ===

[[3twk]], [[3twl]], [[3twm]], [[1pjj]], [[1r2y]], [[1ee8]], [[1k82]], [[1L1Z]], [[1L2B]], [[1L2C]], [[1L1T], [[1L2D]], [[1R2Z]], [[1PM5]], [[1NNJ]], [[1KFV]], [[1PJI]], [[3C58]], [[3VK5]], [[2XZU]], [[2XZF]], [[1TDZ]], [[1XC8]]

=== Nei ===

[[2EA0]], [[2OPF]], [[2OQ4]], [[1Q3C]], [[1Q3B]], [[1Q39]]

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-27T23:01:33Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.

== References ==
<references/>

User:Abbas Raza/Sandbox 1

2014-04-27T23:01:01Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Biological Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T22:59:46Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. The reason being that alpha-B in Neil3 does not align with the corresponding helix in the other Nei families (Figure 2). Additional stabilizing bonds by residues Asp-155, Ile-156, and Ser-158 and neighboring residues Gly-81 and Arg-227 create a restricted movement and hence catalysis of predominately single stranded lesions by MmNEIL3.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
The DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T22:52:59Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145)]].
Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T22:52:12Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G.
[[Image:Alignment_neils.png|thumb|left|300px| '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145).
Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T22:49:54Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G.
[[Image:Alignment_neils.png|thumb|left|300px|]] '''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145). Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T22:49:01Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G.
[[Image:Alignment_neils.png|thumb|left|300px|'''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the �alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145). Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T22:48:27Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G.

[[Image:Alignment neils.png|thumb|left|300px|

'''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the �alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145). Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T22:47:46Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. [[Image:Alignment neils.png|thumb|left|300px|'''Figure 2. Alignment of the alpha-B-alpha-C.''' Analysis of the �alpha-B-alpha-C from MmuNeil3 with that of NEIL1 (residues 126–151) and bacteriial nei (residue 113–145). Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 3. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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/>

File:Alignment neils.png

2014-04-27T22:38:51Z

Abbas Raza: uploaded a new version of "Image:Alignment neils.png"

File:Alignment neils.png

2014-04-27T22:36:06Z

Abbas Raza:

User:Abbas Raza/Sandbox 1

2014-04-27T22:21:30Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 2. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T21:55:46Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, Fa pyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL2 is similar to NEIL3 in terms of substrates attacked whereas NEIL1 on the other hand, prefers double stranded DNA lesions. The idea of having multiple enzymes to repair the same lesion confirms that NEIL3 might act as a backup line of defense against oxidative damage.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 2. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.

== Disease ==
Experiments with knock-out NEIL3-/-mice showed that the animals were viable and fertile and had no obvious contrasting phenotype<ref>PMID: 16428305</ref> . However, later studies have reported memory defects and reduced anxiety like symptoms in C57BL/6 mice indicative of impaired proliferatived neural cells but no defects in fertility or viability<ref>PMID: 22065741</ref>. This adds to the idea that the biological function of NEIL3 is not exclusively restricted to DNA repair. High expression in spleen and bone marrow hints a role in immune system.
== 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:Abbas Raza/Sandbox 1

2014-04-27T21:25:47Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, FapyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>. NEIL1 on the other hand, prefers double stranded DNA lesions.
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 2. DNA damages repaired by NEIL3''']]

== NEIL3 expression and localisation ==
The expression of NEIL3 is tissue specific with high levels in spleen, testis, bone marrow and brain. Transfection of Hela cell lines localised this protein to nucleus but not in mitochondria<ref>PMID: 16428305</ref>. The protein levels fluctuate during cell cycle like other DNA glycosylases with highest expression during G2 phase of cell cycle<ref>PMID: 18195366</ref>.
== 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:Abbas Raza/Sandbox 1

2014-04-27T21:08:58Z

Abbas Raza:

='''NEIL3: a DNA repair glycosylase from ''Mus musculus'''''=

<Structure load='3w0f' size='400' frame='true' align='right' caption=''''Crystal structure of mouse Endonuclease VIII-LIKE 3 neil3 protein (mNEIL3)pdb id 3w0f'''' scene='Insert optional scene name here' />

[[Image:NEIL3 domains.png|thumb|left|300px|'''Figure 1. Mouse NEIL3''' (A) Cartoon representation of NEIL3 domains (pdb id 3w0f) (B) full length MmNEIL3 protein showing additional DNA binding domains (RANbp and GRF) not found in other neil/fpg proteins and (C)Comparison of NEIL3 proteins with other fpg/neil members, the color coding follows the same domains as in (B)]]

This protein is a unique member of DNA glysosylases, family of base excision repair enzymes that show preference for both oxidative purines and pyrimidine lesions. For a description of all known DNA glycosylases and their families see the wikepedia page on DNA glycosylases [[http://en.wikipedia.org/wiki/DNA_glycosylase]]. Originally identified through in-silico studies from Wallace, Mitra and Seeger group back in 2002<ref>PMID: 12509226</ref>,<ref>PMID: 11904416</ref>,<ref>PMID: 12433996</ref> the crystallisation of NEIL3 remained challenge for almost a decade due to the difficulty in getting a stabilized form of the protein for crystallization until a truncated version was crystallized in 2013 <ref>PMID: 23313161</ref> and the crystal structure publlished as <scene name='58/583383/3w0f/2'>3W0F</scene>.

NEIL3 proteins are almost twice the size of other Fpg/Nei family members (Figure 1C). This protein belongs to alpha/beta[[http://en.wikipedia.org/wiki/Protein_fold_class]] category of proteins with the following secondary structure elements: <scene name='58/583383/3wof_3d_structure/24'>alpha-A(3-16)</scene>, <scene name='58/583383/3wof_3d_structure/27'>beta-1(23-27)</scene>, <scene name='58/583383/3wof_3d_structure/26'> beta-2(73-79)</scene>, <scene name='58/583383/3wof_3d_structure/28'> beta-3(82-87)</scene>, <scene name='58/583383/3wof_3d_structure/29'> beta-4(90-96)</scene>, <scene name='58/583383/3wof_3d_structure/30'>beta-5(101-104)</scene>,<scene name='58/583383/3wof_3d_structure/31'>beta-6(119-123)</scene>,<scene name='58/583383/3wof_3d_structure/32'>beta-7(127-131)</scene>,<scene name='58/583383/3wof_3d_structure/33'>beta-8(133-139)</scene>,<scene name='58/583383/3wof_3d_structure/34'>alpha-B(140-150)</scene>, <scene name='58/583383/3wof_3d_structure/35'>alpha-C(162-171)</scene>, <scene name='58/583383/3wof_3d_structure/36'>alpha-D(177-182)</scene>,<scene name='58/583383/3wof_3d_structure/37'>alpha-E(192-202)</scene>,<scene name='58/583383/3wof_3d_structure/38'>alpha-F(215-238), </scene>,<scene name='58/583383/3wof_3d_structure/39'>beta-9(262-264)</scene>,
<scene name='58/583383/3wof_3d_structure/40'>beta-10(273-275)</scene>. The beta strands form a two-layered <scene name='58/583383/Beta_strands/3'>beta sandwich</scene> at the N-terminus in which each layer is composed of four anti-parallel beta strands. The C terminus has a Helix 2 turn Helix (H2TH) motif formed by <scene name='58/583383/H2th/2'>alpha-C and D</scene> and a canonical
<scene name='58/583383/Zinc_finger/2'>zinc finger motif</scene> formed by the interconnecting loop between beta strands-9 and 10. In contrast to other Fpg/nei members, NEIL3 has two additional DNA binding domains at their C-terminus: one Ran binding protein (RanBP2)-type zinc finger motif and two identical GRF-zinc finger motif. The catalytic residue of MmuNEILL3 is a <scene name='58/583383/3wof_3d_structure/41'>Val-2</scene> rather than a proline as for other Fpg/nei members but serves the same purpose in catalysis and is surrounded by <scene name='58/583383/3wof_3d_structure/42'>R272, Y250 C247, F233,I-194 and M99</scene> that forms the DNA binding cleft and lesion binding pocket of NEIL3.

----

== '''Function''' ==

MmuNeil3 is a bifunctional DNA glycosylase that exhibits a broad substrate recognition spectrum (Sp, Gh, FapyG, FapyA, MeFapyG, DHU, DHT, 5-OHU, 5-OHC,5-OHMH, Tg, 8-oxoA, AP) but not 8-oxo-G. Additionally, the DNA structures attacked most often are large bubble and single stranded DNA and least duplex DNA<ref>PMID: 23274422</ref>
[[Image:Dna_lesions.png|thumb|left|300px|'''Figure 2. DNA damages repaired by NEIL3''']]

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/>

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