Proteopedia - User contributions [en]

T-box proteins

2012-06-04T19:10:14Z

Helen Ginn: /* T-box family members in ''Homo sapiens'' */

{{STRUCTURE_4a04| PDB=4a04 | SIZE=400| SCENE= |right|CAPTION=Human TBX1 complex with DNA, [[4a04]] }}

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of '''T-box proteins''' are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''. For details on individual T-box proteins see [[TBX1]], [[TBX3]], [[TBX5]], [[TBX15]]. See also [[Transcription and RNA Processing]].

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and [[TBX3]] and [[TBX5]] on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
| Crystal structure solved ([[4a04]])
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=3D structures of T-box protein=

[[4a04]] – hTBX1 T-box domain - human 
[[1h6f]] - hTBX3 T-box domain + DNA 
[[2x6u]] – hTBX5 T-box domain 
[[2x6v]] – hTBX5 T-box domain + DNA

=Additional Resources=
For additional information, see: [[Transcription and RNA Processing]]
 

=References=

* Current Opinion in Genetics & Development 1997, 7:474-480;
* Gene 258 (2000) 15–29;
* American Journal of Medical Genetics Part A 140A:1407–1413 (2006);
* Genome Biology 2002, 3(6):reviews3008.1–3008.7;

T-box proteins

2012-06-04T19:09:49Z

Helen Ginn: /* T-box family members in ''Homo sapiens'' */

{{STRUCTURE_4a04| PDB=4a04 | SIZE=400| SCENE= |right|CAPTION=Human TBX1 complex with DNA, [[4a04]] }}

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of '''T-box proteins''' are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''. For details on individual T-box proteins see [[TBX1]], [[TBX3]], [[TBX5]], [[TBX15]]. See also [[Transcription and RNA Processing]].

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and [[TBX3]] and [[TBX5]] on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
| Crystal structure solved ([[4a04]]
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=3D structures of T-box protein=

[[4a04]] – hTBX1 T-box domain - human 
[[1h6f]] - hTBX3 T-box domain + DNA 
[[2x6u]] – hTBX5 T-box domain 
[[2x6v]] – hTBX5 T-box domain + DNA

=Additional Resources=
For additional information, see: [[Transcription and RNA Processing]]
 

=References=

* Current Opinion in Genetics & Development 1997, 7:474-480;
* Gene 258 (2000) 15–29;
* American Journal of Medical Genetics Part A 140A:1407–1413 (2006);
* Genome Biology 2002, 3(6):reviews3008.1–3008.7;

T-box proteins

2012-06-04T19:09:17Z

Helen Ginn: /* T-box family members in ''Homo sapiens'' */

{{STRUCTURE_4a04| PDB=4a04 | SIZE=400| SCENE= |right|CAPTION=Human TBX1 complex with DNA, [[4a04]] }}

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of '''T-box proteins''' are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''. For details on individual T-box proteins see [[TBX1]], [[TBX3]], [[TBX5]], [[TBX15]]. See also [[Transcription and RNA Processing]].

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and [[TBX3]] and [[TBX5]] on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
| Crystal structure solved
| DiGeorge syndrome
| Crystal structure solved
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=3D structures of T-box protein=

[[4a04]] – hTBX1 T-box domain - human 
[[1h6f]] - hTBX3 T-box domain + DNA 
[[2x6u]] – hTBX5 T-box domain 
[[2x6v]] – hTBX5 T-box domain + DNA

=Additional Resources=
For additional information, see: [[Transcription and RNA Processing]]
 

=References=

* Current Opinion in Genetics & Development 1997, 7:474-480;
* Gene 258 (2000) 15–29;
* American Journal of Medical Genetics Part A 140A:1407–1413 (2006);
* Genome Biology 2002, 3(6):reviews3008.1–3008.7;

T-box proteins

2012-06-04T19:08:41Z

Helen Ginn: /* T-box family members in ''Homo sapiens'' */

{{STRUCTURE_4a04| PDB=4a04 | SIZE=400| SCENE= |right|CAPTION=Human TBX1 complex with DNA, [[4a04]] }}

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of '''T-box proteins''' are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''. For details on individual T-box proteins see [[TBX1]], [[TBX3]], [[TBX5]], [[TBX15]]. See also [[Transcription and RNA Processing]].

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and [[TBX3]] and [[TBX5]] on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
|
| DiGeorge syndrome
| Crystal structure solved
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=3D structures of T-box protein=

[[4a04]] – hTBX1 T-box domain - human 
[[1h6f]] - hTBX3 T-box domain + DNA 
[[2x6u]] – hTBX5 T-box domain 
[[2x6v]] – hTBX5 T-box domain + DNA

=Additional Resources=
For additional information, see: [[Transcription and RNA Processing]]
 

=References=

* Current Opinion in Genetics & Development 1997, 7:474-480;
* Gene 258 (2000) 15–29;
* American Journal of Medical Genetics Part A 140A:1407–1413 (2006);
* Genome Biology 2002, 3(6):reviews3008.1–3008.7;

User:Helen Ginn

2010-09-06T13:39:15Z

Helen Ginn:

Undergraduate Student in Biochemistry at Oxford University.
 Website: [[http://www.cmol.org.uk/index.php?proteopedia www.cmol.org.uk]]

=A link=

[[/Workbench]] I am a link to my workbench

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

User:Helen Ginn

2010-09-06T13:38:00Z

Helen Ginn:

Undergraduate Student in Biochemistry at Oxford University.
 Website: [[http://www.cmol.org.uk/index.php?proteopedia|www.cmol.org.uk]]

=A link=

[[/Workbench]] I am a link to my workbench

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

User:Helen Ginn

2010-09-06T13:37:44Z

Helen Ginn:

Undergraduate Student in Biochemistry at Oxford University.
 Website: [[http://www.cmol.org.uk/index.php?proteopedia]]

=A link=

[[/Workbench]] I am a link to my workbench

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

User:Helen Ginn

2010-09-06T13:36:26Z

Helen Ginn:

Undergraduate Student in Biochemistry at Oxford University.
 Website: http://www.cmol.org.uk/index.php?proteopedia

=A link=

[[/Workbench]] I am a link to my workbench

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

User:Helen Ginn

2010-09-06T13:35:59Z

Helen Ginn:

Undergraduate Student in Biochemistry at Oxford University.
 Website: <a href="http://www.cmol.org.uk/index.php?proteopedia=yes">www.cmol.org.uk</a>

=A link=

[[/Workbench]] I am a link to my workbench

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

User:Helen Ginn

2010-09-02T12:38:39Z

Helen Ginn:

Undergraduate Student in Biochemistry at Oxford University.
 Website: www.cmol.org.uk

=A link=

[[/Workbench]] I am a link to my workbench

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

User:Helen Ginn

2010-08-19T11:54:19Z

Helen Ginn: Adding workbench

Undergraduate Student in Biochemistry at Oxford University.
Website: www.ribosome.co.uk

=A link=

[[/Workbench]] I am a link to my workbench

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

TBX1

2010-07-22T11:31:24Z

Helen Ginn: Adding ref

=Introduction=

==Insights into TBX1==

The gene locus for TBX1 in humans is on 22q11.2 (chromosome 22). This is the region of a common mutation (named 22q11.2 deletion syndrome) characterised by a deletion of 3Mb of DNA (30 genes) leading to the phenotype of the DiGeorge syndrome. By examining patients with DiGeorge syndrome but without the 3Mb deletion syndrome, tbx1 has been flagged as one which has a high mutation rate, and is therefore implicated in DiGeorge syndrome. However, mutations in the protein TBX1 alone do not implicate mental retardation. Mutants of TBX1 are responsible for at least five major phenotypes:

* Conotruncal anomaly face
* Cardiac defects
* Thymic hypoplasia
* Velopharyngeal insufficiency with cleft palate
* Parathyroid disfunction with hypocalcaemia

TBX1 has been found to be haploinsufficient, i.e. dosage-specific: mice which carry too few or too many copies of TBX1 typically show most of the signs of DiGeorge syndrome. However, TBX1 may not be the only implicated gene: Crkl mutations causes some of the DiGeorge phenotype abnormalities.

The TBX1 gene consists of twelve exons: 1-8, 9A, 9B, 10 and 9C, and has three alternative spliced forms of the gene. Thus, when screening for mutants the protein must be screened in all three alternative splice forms. One example of such a screening is for the -39 C→T mutation through a technique known as ARMS (amplification refractory mutation system). A screening of 38 patients with DiGeorge syndrome without the deletion uncovered this mutant. A functional analysis of this mutation is discussed below.

=Functions and pathways of TBX1=

TBX1 and CRKL proteins interact in a dose dependent manner during development. In mice, Tbx1 activates the transcription of an Fgf10 promoter dependent on a T-box binding element (TBE). Fgf8 has also been postulated as a possible target of Tbx1. Transcription of TBX1 in humans depends on an enhancer with a forkhead binding site responsive to Foxc1, Foxc2 and Foxa2, but links in these pathways are uncertain.

The molecular basis of dosage sensitivity is unknown, however it is thought that activation requires heterodimerisation but overexpression leads to homodimerisation (producing an inactive transcription factor).

=Known malfunctional mutations=

* Lysine 411 → Proline in exon 9C
* tbx1 1223delC (eliminates nuclear localisation signal and produces frameshift for 51 codons)
* [[#-39C → T|-39C → T]] (exon 2) - lies within untranslated region and affects secondary structure of mRNA
* Phenylalanine 148 → Tyrosine - conserved residue in the T-box domain
* Glycine 310 → Serine (conserved residue)
* 1274-1281 delACTATCTC → translational frameshift mutation

==-39C → T==

The -39C → T mutant change affects the secondary structure of the mRNA. It lies outside of the 129 bp 5'-UTR, which ordinarily contains 76% GC content. Molecular modelling predicts a stable secondary structure for the wild-type TBX1, but the presence of T instead of C at -39 reduces the stability of this fold, reuslting in a different optimal folding from that of the wild type. Using luciferase as a marker, experiments showed that this mutation greatly increases the amount of TBX1 present in the cell by about 2-fold. This results in the phenotype caused by overexpression of TBX1.

==tbx1 1223delC==

The F148Y and G310S equivalent mutations in mice are still able to activate transcription at nearly the same capacity as the wild-type Tbx1 using a luciferase reporter construct. However, the Tbx1delC mutant has almost the same activation activity as the control used. When the Tbx1delC mutant was examined for subcellular localisation, it was found that it was localised almost entirely to the cytoplasm. The Tbx1delC mutation results in a frameshift of 51 codons before a premature stop codon, with 86 residues missing from Tbx1delC which are normally found in wild-type Tbx1 Deletion of 31 residues from the C-terminus of wild-type Tbx1 results in a truncated protein which does localise correctly to the nucleus. However, deletion of 86 residues results in a truncated protein which localises to the cytoplasm. Thus, the idea of an NLS present in the C-terminus of Tbx1 is likely.

This NLS has been tracked down to a 12-residue motif present in the C-terminus by a series of further deletions fused to GFP and β-galactosidase. This fragment spans residues 415-426 inclusive. There is no significant homology to previously identified NLS sequence. A proline-rich sequence containing the motif BPYPXPB, where B is a basic amino acid, is a conserved sequence throughout Tbx1, Tbx10 and Brachyury. Mutations of R417A and Y421 of the wild-type protein combined resulted in a reduced nuclear localisation signal. The proline residues, although conserved, did not produce this effect.

Tbx1delC also results in the disruption of a transactivation domain.

==References==

* Human Molecular Genetics (2005) 14:7
* Current Opinion in Genetics & Development (2005) 15:279-284

TBX1

2010-07-22T11:29:50Z

Helen Ginn: adding tbx1 1223delC info

Proteopedia:Table of Contents

2010-07-12T13:57:25Z

Helen Ginn: Adding yet more T-box proteins

This guide to the contents of Proteopedia is maintained manually (not automatically generated) and so is inevitably incomplete. Please be sure to use the [[Help:Searching|search slots at the left]] if you don't find what you are looking for below.

<big>
{{#tree:id=siteTree|openlevels=1|close=top|open=top|

* Introduction to Structural Biology
** See [[About Macromolecular Structure]]
** Water

*** [[Water in macromolecular models|Water in Macromolecular Models]]
** Key Chemical Concepts for Structural Biology

*** [[Amino Acids]]
*** [[Cation-pi interactions]]
*** [[Hydrogen bond]]
*** [[Hydrogen in macromolecular models|Hydrogen in Macromolecular Models]]
*** [[Isoelectric point]]
*** [[Salt bridges]]

* Biomolecules
** [[About Macromolecular Structure]]

** Nucleotides, Nucleic Acids and Genetic Information
*** DNA
**** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]

** Amino Acids
*** [[Amino Acids]]
*** [[Selenocysteine]]
** Proteins, Primary Structure
*** [[Conservation, Evolutionary]]
*** [[Isoelectric point]]

** Proteins, Three-Dimensional Structure
*** [[User:Tommie_Hata/Protein_Structure_Tutorial]]
*** [[S347/The four tiers of protein structure]]
*** [[Secondary structure]]
*** Protein structural motifs
**** [[User:James D Watson/Structural Templates]]

*** Protein Misfolding
**** [[Prion protein]]
**** [[A Physical Model of the Structure of GNNQQNY from Yeast Prion Sup35]]

** Colored Proteins & those that Change Color
*** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
*** [[Dronpa]]
*** [[Factor IX]]

** DNA Binding Proteins
*** [[Helix-turn-helix motif]]
*** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

** Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies
*** Antibodies
**** [[IgA]]
**** [[Epitopes]]
**** [[Major Histocompatibility Complex Class I]]
*** [[Calmodulin in motion]]
*** [[Myoglobin]]
*** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]
*** [[Kinesin-5]]
** Lipids and Biological Membranes
** Lipid Binding Proteins
*** [[CRABP I ( Cellular Retinoic Acid Binding Protein )]]
** Membrane Transport Proteins
*** [[A Physical Model of the β2-Adrenergic Receptor]]
***[[Glutamate receptor (GluA2)|Glutamate Receptor]]
*** [[Lactose Permease]]
*** [[Proton Channels]]
*** [[Ion Channels]]
**** [[M2 Proton Channel]]
**** [[Voltage-gated calcium channels]]
****[[Glutamate receptor (GluA2)|Glutamate Receptor]]
*** [[Mechanosensitive channels: opening and closing]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]

** Prions and Intrinsically Disordered Proteins
*** [[Prion protein]]
*** [[Doppel]]
*** [[Intrinsically Disordered Protein]]

** Toxins
*** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

** Mitosis, Meiosis and Cargo Transport Proteins
*** [[Kinesin-5]]

** Viruses
*** [[Suppression of RNA Silencing by Viruses]]
*** Filamentous bacteriophage
**** [[G3p]] - minor coat protein found on the surface of filamentous bacteriophage
*** HIV
**** [[HIV-1 protease]]
**** [[HIV-1 Gag]]
**** [[HIV-1 Gag Recruitment of Tsg101 and the Viral Budding Process]]
**** [[User:Eric Martz/Molecular Playground/HIVDrug]]
*** Herpes Simplex Virus
**** [[Herpes Simplex Virus Thymidine Kinase]]
*** Influenza
**** [[Influenza hemagglutinin]]
**** [[Avian Influenza Neuraminidase, Tamiflu and Relenza]]

* Colored Proteins & those that Change Color
** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
** [[Dronpa]]
** [[Factor IX]]

* DNA Binding Proteins
** [[Helix-turn-helix motif]]
** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

* Enzymes
** Enzymatic Catalysis
*** Acid-beta-glucosidase
**** reHuman Acid-beta-glucosidase made in CHO cells [[1ogs]]
**** reHuman Acid-beta-glucosidase made in CHO cells bound to conduritol B epoxide [[1y7v]]
**** reHuman Acid-beta-glucosidase made in carrot cells complexed with N-butyl-deoxynojirimycin [[2v3d]]
**** Velaglucerase Alfa [[2wkl]]
*** Acid Proteases
**** [[HIV-1 protease]]

**** [[Streptomyces griseus Aminopeptidase (SGAP)]]; [[Aminopeptidase]]
*** [[Aconitase]]
*** Cysteine Proteases
*** [[Hen Egg-White (HEW) Lysozyme]]
*** [[Choline Oxidase]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Metalloproteases]]
**** [[Matrix metalloproteinases]]
*** Oxidoreductases
**** [[NADH quinone oxidoreductase ]]
*** [[Phosphofructokinase %28PFK%29]]
*** [[Pyruvate phosphate dikinase]]
*** [[Serotonin N-acetyltransferase]]
*** Serine Hydrolases
**** [[Acetylcholinesterase]] (AChE)
***** [[Acetylcholine]]
***** [[Flexibility of aromatic residues in acetylcholinesterase]]
***** [[AChE inhibitors and substrates]]
****** [[1eve]] AChE-Aricept complex; [[1eve (Arabic)]]; [[1eve (Chinese)]]; [[1eve (Italian)]]; [[1eve (Russian)]]; [[1eve (Spanish)]]; [[1eve (Turkish)]]
****** [[AChE bivalent inhibitors]]
**** [[Tobacco Etch Virus (TEV) Protease]]
*** [[Serine Protease]]
**** [[Trypsin]]
*** [[Triose Phosphate Isomerase]]
** Enzyme Inhibitors
*** [[Alpha-1-antitrypsin]]
** Enzyme Kinetics, Inhibition, and Control
***[[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
** Biochemical Signaling
*** [[Nitric oxide synthase]], [[NOS structures]]
*** [[Recoverin, a calcium-activated myristoyl switch]]
*** [[Bcl-2]]
*** [[C-Myc]]
*** [[C-di-GMP signaling]]

** Enzymes - Molecular Machines
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Pyruvate phosphate dikinase]]

* Fibrous Proteins
** [[Coiled coil]]
** [[Collagen]]

* Membrane Transport Proteins
** [[A Physical Model of the β2-Adrenergic Receptor]]
** [[Glutamate receptor (GluA2)|Glutamate Receptor]]
** [[Lactose Permease]]
** [[Proton Channels]]
** [[Ion Channels]]
*** [[M2 Proton Channel]]
*** [[Voltage-gated calcium channels]]
** [[Mechanosensitive channels: opening and closing]]
** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]

* Myoglobin & Hemoglobin
** [[Myoglobin]]
** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]

* Nervous System Proteins

** [[Acetylcholinesterase]] (AChE)
*** [[Acetylcholine]]
*** [[Flexibility of aromatic residues in acetylcholinesterase]]

*** AChE inhibitors (In Different Languages)
**** [[1eve]] AChE-Aricept complex, [[1eve (Arabic)]], [[1eve (Chinese)]], [[1eve (Italian)]], [[1eve (Russian)]], [[1eve (Spanish)]], [[1eve (Turkish)]]
**** [[1vot]] AChE-Huperzine A complex, [[1vot (Chinese)]]

*** Acetylcholinesterase - AChE native
**** [[3lii]] – hAChE - recombinant human
**** [[1ea5]], [[2ace]] – ''Tc''AChE – trigonal – ''Torpedo californica''
**** [[2j3d]] – ''Tc''AChE – monoclinic
**** [[1w75]] – ''Tc''AChE – orthorhombic
**** [[1eea]] – ''Tc''AChE – cubic
**** [[2vt6]], [[2vt7]] – ''Tc''AChE – different dosage
**** [[1qid]] to [[1qim]] - ''Tc''AChE synchrotron radiation damage
**** [[1j06]], [[1maa]] – mAChE - mouse
**** [[1qo9]] – ''Dm''AChE - ''Drosophila''
**** [[1c2o]], [[1c2b]] – electrophorus AChE – Electric eel

*** AChE active site inhibitors conjugating at the bottom of the active site gorge
**** [[2w9i]] – ''Tc''AChE + methylene blue
**** [[2wls]] – MosAChE + AMTS13
**** [[2vq6]] – ''Tc''AChE + 2-PAM
**** [[2j3q]] – ''Tc''AChE + Thioflavin T
**** [[2ha0]] – mAChE + ketoamyltrimethylammonium
**** [[2h9y]] – mAChE + TMTFA
**** [[1gpk]], [[1gpn]], [[1vot]] – ''Tc''AChE + huperzine
**** [[1gqr]] – ''Tc''AChE + rivastigmine
**** [[1gqs]] – ''Tc''AChE + NAP
**** [[1e66]] – ''Tc''AChE + huprine
**** [[1dx4]], [[1qon]] – ''Dm''AChE + tacrine derivative
**** [[1oce]] – ''Tc''AChE + MF268
**** [[1ax9]], [[1ack]] – ''Tc''AChE + edrophonium
**** [[1amn]] – ''Tc''AChE + TMTFA
**** [[1acj]] – ''Tc''AChE + tacrine

*** AChE peripheral site inhibitors conjugating at the surface of the protein
**** [[1ku6]] - mAChE + fasciculin 2
**** [[1ku6]], [[1mah]] - mAChE + fasciculin 2
**** [[1j07]] - mAChE + decidium
**** [[1n5m]] - mAChE + gallamine
**** [[1n5r]] - mAChE + propidium
**** [[1b41]], [[1f8u]] - hAChE + fasciculin 2
**** [[1fss]] - TcAChE + fasciculin 2

*** AChE bis inhibitors spanning the active site gorge
**** [[AChE bivalent inhibitors]]
**** [[3i6m]] – ''Tc''AChE + N-piperidinopropyl galanthamine
**** [[3i6z]] - ''Tc''AChE + saccharinohexyl galanthamine
**** [[1zgb]], [[1zgc]] – ''Tc''AChE + tacrine (10) hupyridone
**** [[2w6c]] – ''Tc''AChE + bis-(-)-nor-meptazinol
**** [[2ckm]], [[2cmf]] – ''Tc''AChE + bis-tacrine
**** [[2cek]] – ''Tc''AChE + N-[8-(1,2,3,4-tetrahydroacridin-9-ylthio)octyl]-1,2,3,4-tetrahydroacridin-9-amine
**** [[1ut6]] - ''Tc''AChE + N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1odc]] - ''Tc''AChE + N-4-quinolyl-N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1w4l]], [[1w6r]], [[1w76]], [[1dx6]], [[1qti]] - TcAChE + galanthamine and derivative
**** [[1q83]], [[1q84]] - mAChE + TZ2PA6
**** [[1h22]], [[1h23]] – ''Tc''AChE + bis-hupyridone
**** [[1hbj]] – ''Tc''AChE + quinoline derivativev
**** [[1e3q]] – ''Tc''AChE + bw284c51
**** [[1eve]] – ''Tc''AChE + e2020
**** [[1acl]] – ''Tc''AChE + decamethonium

*** AChE organophosphate inhibitors causing irreversible inhibition
**** [[2wu3]] – mAChE + fenamiphos and HI-6
**** [[2wu4]] – mAChE + fenamiphos and ortho-7
**** [[2jgf]] - mAChE + fenamiphos
**** [[2wfz]], [[2wg0]], [[1som]] - ''Tc''AChE + soman
**** [[2wg1]] - ''Tc''AChE + soman + 2-PAM
**** [[2whp]], [[2whq]], [[2whr]] – mAChE + sarin and HI-6
**** [[2jgg]] - mAChE + sarin
**** [[2jgl]] - mAChE + VX and sarin
**** [[1cfj]] - ''Tc''AChE + sarin, GB
**** [[3dl4]], [[3dl7]] – mAChE + tabun
**** [[2jey]] – mAChE + HLO-7
**** [[2c0p]], [[2c0q]] - mAChE + tabun
**** [[2jez]] - mAChE + tabun + HLO-7
**** [[2jf0]] - mAChE + tabun + Ortho-7
**** [[2jgh]] - mAChE + VX
**** [[1vxo]], [[1vxr]] - ''Tc''AChE + VX
**** [[2jgi]], [[2jgm]] - mAChE + DFP
**** [[1dfp]] - ''Tc''AChE + DFP
**** [[2jgj]], [[2jgk]], [[2jge]] - mAChE + methamidophos
**** [[2gyu]] - mAChE + HI-6
**** [[2gyv]] - mAChE + Ortho-7
**** [[2gyw]] - mAChE + obidoxime

*** AChE substrate analogues mimicking the binding of the substrate acetylcholine
**** [[2ha4]] – mAChE (mutant) + acetylcholine
**** [[2vja]], [[2vjb]], [[2vjc]], [[2vjd]], [[2cf5]] – ''Tc''AChE + 4-oxo-N,N,N-trimethylpentanaminium
**** [[2v96]], [[2v97]], [[2v98]], [[2v99]] – ''Tc''AChE + 1-(2-nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine
**** [[2ha2]] – mAChE + succinylcholine
**** [[2ha3]] - mAChE + choline
**** [[2ha5]] – mAChE (mutant) + acetylthiocholine
**** [[2ha6]] – mAChE (mutant) + succinylthiocholine
**** [[2ha7]] – mAChE (mutant) + butyrylthiocholine
**** [[2ch4]], [[2c58]] – ''Tc''AChE + acetylthiocholine
**** [[2c5g]] – ''Tc''AChE + thiocholine

*** Others…
**** [[2j4f]] – ''Tc''AChE + Hg
**** [[1vzj]] – ''Tc''AChE tetramerization domain
**** [[1jjb]] – ''Tc''AChE + PEG

** [[Acetylcholine binding protein]] (AChBP)
** [[Butyrylcholinesterase]] (BChE)
** [[Glutamate receptor (GluA2)|Glutamate Receptor]]

* Prions and Intrinsically Disordered Proteins
** [[Prion protein]]
** [[Doppel]]
** [[Intrinsically Disordered Protein]]

* Small Iron Sulfur Proteins
** [[Ferredoxin]] (Fd)
*** 2Fe-2S containing ferredoxins
**** [[3hui]] – Fd – ''Rhodopseudomonas palustris''
**** [[2kaj]], [[1dox]], [[1doy]] – SyFd +Ga – Synechocystis – NMR
**** [[1off]] – SyFd
**** [[3gce]] – Fd – Nocardioides aromaticivorans
**** [[2e4p]], [[2e4q]] - Fd – ''Pseudomonas sp.''
**** [[2q3w]], [[1vm9]] - PmFd (mutant) – ''Pseudomonas mendocina''
**** [[2i7f]] - Fd – ''Rhodobacter capsulatus''
**** [[1rfk]] - Fd – Cyanobacterium ''masticogladus laminosus''
**** [[1vck]] - Fd – ''Pseudomonas resinovorans''
**** [[1wri]], [[1frr]] - Fd – Equisetum arvense
**** [[1sjg]] - PmFd– NMR
**** [[1iue]] - Fd– Plasmodium falciparum
**** [[1m2a]] –AeFd – Aquifex aeolicus
**** [[1m2b]], [[1m2d]], [[1f37]], [[1f5b]], [[1f5c]] – AeFd (mutant)
**** [[1l5p]] – Fd – Trichomonas vaginalis
**** [[1i7h]] - Fd – Escherichia coli
**** [[1czp]], [[1qt9]], [[1frd]], [[1fxa]] - aFd– anabaena
**** [[1j7a]], [[1j7b]], [[1j7c]] , [[1qoa]], [[1qob]], [[1qof]], [[1qog]]- aFd (mutant)
**** [[1e0z]] – Fd – Halobacterium salinarium
**** [[1pfd]] – Fd – Petroselinum crispum – NMR
**** [[1a70]] - Fd (mutant) – Spinacia oleracea
**** [[1awd]] - Fd – Chlorella fusca
**** [[2cjn]], [[2cjo]], [[1roe]] – SyFd – NMR
**** [[1rof]] – SyFd – Synechococcus elongates
**** [[1doi]] - Fd – Haloarcula marismortui
**** [[4fxc]] – Fd – Spirulina platensis
**** [[1fxi]] – Fd – Aphanothece sacrum
**** [[3dqy]], [[2qpz]] - Fd – Pseudomonas putida

*** 4Fe-4S containing ferredoxins

**** [[3eun]] – AvFd – Allochromatium vinosum
**** [[3exy]] - AvFd (mutant)
**** [[2vkr]] - Fd+Zn – Acidianus ambivalens
**** [[2z8q]] - PfFd (mutant) – Pyrococcus furiosus
**** [[2fgo]] - Fd– Pseudomonas aeruginosa
**** [[1iqz]], [[1ir0]] - BtFd – Bacillus thermoproteolyticus
**** [[1rgv]] - Fd – Thauera aromatica
**** [[1dax]], [[1dfd]] – DaFd – Desulfovibrio africanus – NMR
**** [[1fxr]] - DaFd
**** [[1vjw]] – Fd – Thermotoga maritima

*** 3Fe-4S containing ferredoxins

**** [[2v2k]] – Fd – Mycobacterium smegmatis
**** [[1wtf]] - BtFd (mutant)
**** [[1sj1]] - PfFd
**** [[1fxd]] - DgFd – Desulfovibrio gigas
**** [[1f2g]] – DgFd – NMR
**** [[1xer]] - Fd – Sulfolobus tokodaii

*** 4Fe-4S+3Fe-4S containing ferredoxins

**** [[1gao]], [[6fdr]], [[7fd1]], [[7fdr]], [[1axq]], [[6fd1]], [[1frh]], **** [[1fri]],[[1frj]], [[1frk]], [[1frl]], [[1frm]], [[1fda]], [[1fdb]], **** [[1fdd]], [[5fd1]], [[1fer]] – AvFd – Azotobacter vinelandii
**** [[1pc4]], [[1pc5]], [[1g6b]], [[1g3o]], [[1ff2]], [[1b0v]], [[1d3w]], **** [[1b0t]], [[1a6l]], [[1ftc]], [[1frx]], [[2fd2]], [[1fd2]] - AvFd (mutant)
**** [[1h98]] – Fd – Thermus thermophilus
**** [[1a8p]], [[1bd6]] - BsFd – Bacillus schlegelii – NMR

*** 4Fe-4S+4Fe-4S containing ferredoxins

**** [[1dur]] – Fd – Peptoniphilus asaccarolyticus
**** [[1bwe]], [[1bqx]] - BsFd (mutant) – NMR
**** [[2fdn]], [[1fca]] , [[1fdn]]- Fd – Clostridium acidi-urici
**** [[1blu]] - Fd – Chromatium vinosum
**** [[1clf ]]– Fd – Clostridium pasteurianum – NMR

*** Adrenoredoxin

**** [[2jqr]] – ADR Fd domain (mutant)+cytochrome c (mutant) – yeast – NMR
**** [[2bt6]] – cADR1 modified – cow
**** [[1l6u]], [[1l6v]] – cADR1 – NMR
**** [[1e6e]] – cADR (mutant)+ADR reductase
**** [[1cje]], [[1ayf]] - cADR

*** Putidaredoxin

**** [[1yji]], [[1yjj]], [[1pdx]] – PpPUT – Pseudomonas putida – NMR
**** [[3lb8]] – PpPUT (mutant)+PUT reductase
**** [[1xln]], [[1xlo]], [[1xlp]], [[1xlq]], [[1r7s]], [[1oqq]], [[1oqr]] - PpPUT (mutant)
**** [[1gpx]], [[1put]]- PpPUT (mutant) - NMR

*** Terpredoxin

**** [[1b9r]] – TER – Pseudomonas - NMR

* Toxins
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]
** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

* Diseases
** Cancer
*** [[SRC]]
*** [[Proteins involved in cancer]]

* Evolution
** [[Conservation, Evolutionary]]
** [[Extremophiles]]

* Gene Expression and Replication
** Nucleic Acid Structure
*** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]
*** [[Nucleosomes]]

** DNA Replication, Repair, and Recombination
*** [[DNA Replication,Transcription and Translation]]
*** [[DNA Polymerase I]]
*** [[PcrA helicase]]
*** [[Fpg Nei Protein Superfamily]] - DNA Repair and Base Excision DNA Repair
*** [[Human RecQ-Like protein 1]] - RecQ family of DNA helicases are conserved in from bacteria to man
*** [[Structure of E. coli DnaC helicase loader]]
*** [[1x9n#Crystal Structure of Human DNA Ligase I bound to 5.27-adenylated.2C nicked DNA]]
*** [[Rop protein]]

** Transcription and RNA Processing
*** T-box family
**** [[T-box proteins]]
**** [[Brachyury]]
**** [[TBX1]]
**** [[TBX3]]
**** [[TBX5]]
**** [[TBX15]]
*** [[C-Myc]]
*** [[Lac repressor]]
*** [[Reverse transcriptase]]
*** [[TATA-Binding Protein]]
*** [[RSP1275]]
*** [[Transcription Termination Factor Rho]]

** Protein Synthesis
*** [[1fnm|Ef-G]]
*** [[Ribosome]]
*** [[Large Ribosomal Subunit of Haloarcula|Large Ribosomal Subunit]]
*** [[Ribosomal back translocase|ribosomal back translocase, Escherichia coli LepA]]
*** [[SelB Recognition]]
*** [[1ehz|tRNA]]

** Regulation of Gene Expression
*** [[Lac repressor]]
*** [[Irr]] (Iron Response Regulator )
*** Oncogenes
**** [[P53]]
**** [[SRC]]
*** [[Tangible Models of Cdc42 Interacting With Intersectin]]

* Immune System
** Antibodies
*** [[IgA]]
*** [[Epitopes]]
** [[Major Histocompatibility Complex Class I]]
*** [[Human beta two microglobulin]]

* Metabolism
** Introduction to Metabolism

** Glucose Catabolism
*** [[Triose Phosphate Isomerase]]
***[[Phosphofructokinase %28PFK%29]]

** Glycogen Metabolism and Gluconeogenesis
*** [[Phosphoglucose isomerase]]
*** [[Calmodulin in motion]]
*** [[Biotin Protein Ligase]]

** Citric Acid Cycle
*** [[Aconitase]]

** Electron Transport and Oxidative Phosphorylation
*** [[NADH quinone oxidoreductase ]]

** Photosynthesis
*** [[Photosystem II]]
*** [[Ribulose-1,5-bisphosphate carboxylase/oxygenase]]
*** [[PrrA in Rhodobacter sphaeroides]]
*** [[Pyruvate phosphate dikinase]]

** Lipid Metabolism
*** [[Acid-beta-glucosidase]]
** Amino Acid Metabolism
*** [[Aromatic amino acid hydroxylases]]
*** [[Phenylalanine hydroxylase]]
*** [[Tyrosine hydroxylase]]
*** [[ATP Phosphoribosyl Transferase]]
*** [[Isochorismate pyruvate lyase]]
** Mammalian Fuel Metabolism: Integration and Regulation
** Nucleotide Metabolism
*** [[Dihydrofolate reductase]]

* Methods of Structure Determination
** X-ray
*** [[X-ray crystallography]]
**** [[Asymmetric Unit]]
**** [[Biological Unit]]
**** [[Electron density maps]]
*** SAXS
** NMR
*** [[NMR Ensembles of Models]]
** Electron Microscopy

* Methods of Structure & Sequence Analysis
** Structural Analysis & Visualization
*** [[CPK]] - Corey-Pauling-Koltun spacefilling molecular models and color scheme for elements
*** [[Chime]]
*** Jmol
**** [[S347/Visualising protein structure|Visualising Protein Structure]] - Introduction to Jmol
**** [[FirstGlance in Jmol]]
*** [[User:Wayne Decatur/Teaching Proteopedia|Teaching Proteopedia]]
*** [[User:Wayne Decatur/Generate Unfolded Structures|Generate Unfolded Structures]]
*** Homology Model
**** [[User:Wayne Decatur/Homology Modeling|Homology Modeling]]
**** [[User:Emi Nakayama/TRIM5a Homology Models|TRIM5a Homology Models]] - Differences in models as a function of their templates
*** [[DRuMS]] - set of standard color schemes for macromolecular visualization

** Sequence Analysis
*** [[User:Wayne Decatur/Sequence analysis tools|Sequence Analysis Tools]]

* Model Structures
** See [[Theoretical models]]
** [[African Malaria Mosquito Acetylcholinesterase]]
** [[Structure of E. coli DnaC helicase loader]]
** [[User:Yuan-Ping Pang/HAB•BoNTAe]]

* Miscellaneous
** [[Molecular Playground]]
** [[Research Groups]]
}}
</big>

TBX5

2010-07-12T13:54:47Z

Helen Ginn: Formatting was haywire, now it is calm

=Introduction=

TBX5 is a protein of which mutants can cause the Holt-Oram syndrome. It has been crystallised twice, one with and one without the corresponding DNA. It is different from the [[TBX3]] and [[Brachyury]] structures in the way that it dimerises, and that it has been bound to a half-site rather than a full palindromic site. The difference in dimerisations calls into question whether these proteins dimerise naturally or, as their in vivo predicted binding sites suggest, bind monomerically to the DNA. These proteins generally do not dimerise in conserved regions.

A bioinformatic search suggests that two nuclear localisation signals exist, one in the T-box domain and one in the transactivation domain.

=Crystal structure=

Lone TBX5 crystallised in the P212121 space group to 1.9 Å resolution, whereas that with the half-site DNA crystallised to 2.2 Å resolution in the P6122 space group. TBX5 has a very similar structure to those solved structures of TBX3 and Brachyury, and superimposing TBX3 and TBX5 give a root mean standard deviation of 2.1 Å over 174 atoms. These structures will be discussed in turn.

==TBX5 bound to DNA ([[2x6v]])==

The DNA for this crystal structure was taken from the ANF promoter, a known binding site for T-box proteins. Although there is only room for one TBX5 monomer to bind to a half-site, two TBX5 monomers were seen in the asymmetric unit, with the other interacting with the DNA-bound form
in the asymmetric unit through two contact regions. A β sheet conntects these through strand G and G' (of each monomer), involving eight amino acids. This is additionally stabilised by a disulphide bridge from Cys202 of both proteins: this residue is not conserved which may explain why TBX3 and Brachyury do not adopt this dimerisation state. Analytical centrifugation suggests that TBX5 is a monomer when in solution and bound to DNA, and the observed dimerisation is simply an artifact of crystallising the protein. The second, more minor contact site involves a loop region which is predicted to be disordered by the RONN algorithm in the monomeric state, and extends from residues K126-P132 (sequence KAEPAMP).

The TBX5 310 helix at the C-temrinus takes part in recognising DNA. Helix 3, like in Brachyury, interacts strongly with DNA. Residues F232 and F236 are positioned for direct interactions with the minor groove.

==Lone TBX5 ([[2x6u]])==

Lone TBX5 crystallised with just one TBX5 in the asymmetric unit, failing to form the disulphide bridge as seen in the first crystal structure. However, the region which formed the minor contacts with the other TBX5 in the DNA-bound crystal structure is disordered in this structure, as predicted by the RONN algorithm. Similar disordered predictions are seen in Brachyury, although in the DNA-bound state this has a well-defined electron density (this could be stabilised by the crystal packing, however) and is part of a long loop region. The 310C helix is also disordered in the apo-form of TBX5.

TBX5

2010-07-12T13:54:26Z

Helen Ginn: New page! Hurrah

=Introduction=

TBX5 is a protein of which mutants can cause the Holt-Oram syndrome. It has been crystallised twice, one with and one without the corresponding DNA. It is different from the [[TBX3]] and

[[Brachyury]] structures in the way that it dimerises, and that it has been bound to a half-site rather than a full palindromic site. The difference in dimerisations calls into question whether

these proteins dimerise naturally or, as their in vivo predicted binding sites suggest, bind monomerically to the DNA. These proteins generally do not dimerise in conserved regions.

A bioinformatic search suggests that two nuclear localisation signals exist, one in the T-box domain and one in the transactivation domain.

=Crystal structure=

Lone TBX5 crystallised in the P212121 space group to 1.9 Å resolution, whereas that with the half-site DNA crystallised to 2.2 Å resolution in the P6122 space group. TBX5 has a very similar structure to those solved structures of TBX3 and Brachyury, and superimposing TBX3 and TBX5 give a root mean standard deviation of 2.1 Å over 174 atoms. These structures will be discussed in turn.

==TBX5 bound to DNA ([[2x6v]])==

The DNA for this crystal structure was taken from the ANF promoter, a known binding site for T-box proteins. Although there is only room for one TBX5 monomer to bind to a half-site, two TBX5 monomers were seen in the asymmetric unit, with the other interacting with the DNA-bound form
in the asymmetric unit through two contact regions. A β sheet conntects these through strand G and G' (of each monomer), involving eight amino acids. This is additionally stabilised by a disulphide bridge from Cys202 of both proteins: this residue is not conserved which may explain why TBX3 and Brachyury do not adopt this dimerisation state. Analytical centrifugation suggests that TBX5 is a monomer when in solution and bound to DNA, and the observed dimerisation is simply an artifact of crystallising the protein. The second, more minor contact site involves a loop region which is predicted to be disordered by the RONN algorithm in the monomeric state, and extends from residues K126-P132 (sequence KAEPAMP).

The TBX5 310 helix at the C-temrinus takes part in recognising DNA. Helix 3, like in Brachyury, interacts strongly with DNA. Residues F232 and F236 are positioned for direct interactions with the minor groove.

==Lone TBX5 ([[2x6u]])==

Lone TBX5 crystallised with just one TBX5 in the asymmetric unit, failing to form the disulphide bridge as seen in the first crystal structure. However, the region which formed the minor contacts with the other TBX5 in the DNA-bound crystal structure is disordered in this structure, as predicted by the RONN algorithm. Similar disordered predictions are seen in Brachyury, although in the DNA-bound state this has a well-defined electron density (this could be stabilised by the crystal packing, however) and is part of a long loop region. The 310C helix is also disordered in the apo-form of TBX5.

T-box proteins

2010-07-12T13:52:28Z

Helen Ginn: Removing incorrect things

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of T-box proteins are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''.

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and Tbx3 and Tbx5 on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
|
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=References=

* Current Opinion in Genetics & Development 1997, 7:474-480;
* Gene 258 (2000) 15–29;
* American Journal of Medical Genetics Part A 140A:1407–1413 (2006);
* Genome Biology 2002, 3(6):reviews3008.1–3008.7;

User:Helen Ginn

2010-07-09T08:22:26Z

Helen Ginn: Adding image

Undergraduate Student in Biochemistry at Oxford University.
Website: www.ribosome.co.uk

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

Now try <scene name='User:Helen_Ginn/310c_chaina/1'>zooming in to Chain A</scene>.

[[Image:TBX3_3_labels.png|thumb|left|alt=TBX3 3_10 helix interacting with DNA|TBX3 3_10 helix interacting with DNA.]]

File:TBX3 3 labels.png

2010-07-09T08:21:03Z

Helen Ginn: TBX3 image with labels showing 3_10 helix interacting with DNA

== Summary ==
TBX3 image with labels showing 3_10 helix interacting with DNA
== Licensing ==
{{PD-self}}

User:Helen Ginn

2010-07-09T08:18:26Z

Helen Ginn: Chain A

TBX3

2010-07-08T17:16:01Z

Helen Ginn: adding green link

=Introduction=

TBX3 acts as a repressor and has had its crystal structure solved to 1.7 Å resolution. There are many differences between the solved structure of TBX3 and its homologue, [[Brachyury]]. Secondary structures and quaternary contacts are slightly different. TBX3 independently recognises two halves of a palindromic site whereas Brachyury is stabilised via interactions between the two monomers. Despite this, the T-box domain of TBX3 and the T-box domain of Brachyury can be superimposed with a rmsd of 1.3 Å for 167 atoms.

=Crystal structure=
{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

TBX3 expressed from residues 101 - 291 were viable proteins and were crystallised in space group P212121. These included two monomers and one DNA duplex in the asymmetric unit. The monomers themselves can be superimposed to give an rmsd of 0.5 Å. The largest differences between the TBX3 crystal structure and the T-box domain of Brachyury is between residues 173 and 184, and between strands F and G. Four residues are inserted between F and G and this adopts a 310 conformation.

=Interaction with DNA=

Loops that protrude from one end of the β barrel and the C-terminal helical extension contact both the major and minor grooves of the DNA. Strand B contains residues <scene name='User:Helen_Ginn/310c_arg130-131/1'>Arg130 and Arg131</scene>, and recognises the major groove. Arg130 is the only residue in direct contact with a DNA base in the major groove and recognises N7 and H2O.O6 of guanine (base pair 5) and the corresponding phosphate. Arg131 interacts with the DNA backbone mediated by water.

==gα3 loop interaction with DNA==

The gα3 loop spans the major groove. H3 (Tyr264, Gln265 and <scene name='User:Helen_Ginn/310c_277/3'>Asn277</scene>) form polar contacts to the DNA backbone and hydrophobic contacts to the ribose moiety. There are similar contacts in the crystal structure of Brachyury.

==310 helix interaction with DNA==

The helix 310C, also present in TBX5, contacts DNA in the minor groove and hence widens it. However, overall the DNA is not bent, as seen in other crystal structures of [[T-box proteins]]. The 310 helix interacts with DNA using <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277 (of the preceding loop), F279, K281 and F283.</scene> (See <scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>, <scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>,
<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene> and <scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>).

Brachyury

2010-07-08T12:30:04Z

Helen Ginn:

=Introduction=

Two well-known orthologues of the Homo sapiens T protein are present in mice (Brachyury) and Xenopus laevis (Xbra). The homologue of T in mice, Brachyury, was the first T-box crystal structure to be determined.

=Crystal structure ([[1xbr]])=

The T-box region of the Brachyury protein was crystallised with a 24 bp palindromic DNA duplex as determined by in vitro PCR-based binding selection. It crystallised as a dimer; in one monomer residues 39-221 were visible out of a total of 226 residues, and in the other residues 39-222 were visible. Both monomers were bound to the DNA (unlike in the structure of [[TBX5]]) and interacted through a poorly conserved region of 250 Å2. The N-terminus of 38 residues and C-terminus of 4 residues were disordered in the crystal structure. Nevertheless, the crystallographic structure agrees with DNA footprinting experiments in terms of which bases are protected by the protein.

The core of the monomer is a seven-stranded β-barrel structure reminiscent of the immunoglobulin fold. Hence the T protein belongs to the superfamily of Ig-domain transcription factors. Strand D of the seven-stranded β-barrel is replaced by helix H2, and the strand-connecting regions also contain α-helices. The C-terminal amino acids are α-helical in structure, unlike TBX3 and TBX5 where they form a 310 helix. The dimer interface is mainly formed by the ends of strand C' of both proteins.

==Dimer interface==

Residues Pro125, Asp126 and Pro128 from both monomers are bridged by water molecules and the nitrogen of Asn129 forms a hydrogen-bond to Ser127 of the other subunit. To stabilise the structure a hydrophobic patch formed by Pro128, Phe130 and assisted by Met85 and Val173 exists between the two monomers. Some types of T-box proteins have exchanged amino acids for Met85 (Lys, Arg, His), Val173 (Ala) and Phe130 (Thr) which may not undergo dimer formation.

The Brachyury protein is a monomer in solution and thus only dimerises when in contact with DNA. This is supported by the fact that the contact area is only 250 Å2. Antibodies stabilise the dimer on the DNA, however the molecular mechanism of this is unknown: it is possible that the antibodies stabilise the dimer contacts when present on the DNA.

==Structural aspects of DNA binding==

The loops between the β strands make the important contacts with the DNA. 11 amino acids make polar contacts with the DNA, mainly in the minor groove. Helix H3 and H4 recognise the DNA in the minor groove, where H3 bridges the DNA backbone and is positioned by Tyr196/Asn209 contacts with the phosphates on the edges and hydrophobic contacts between guanine ribose and Ile206 in the middle. H4 points into the minor groove with hydrphobic contacts to base edges/backbone sugars and hydrogen bonds between the Phe211 carbonyl group and N2 of guanine. Note that it can be any amino acid which fills this position (i.e., not conserved), however only guanine is recognised.

It is important to note that H3/H4 is not a helix-turn-helix motif. The angle between the helices is 90° (HTH motifs: 120°) and there are 2 amino acids in the loop (HTH motifs: 4), and it interacts in the minor groove (HTH motifs interact in the major groove). The T-domain is very similar to the NF-κB p50, and superimposing these shows the major groove recognition carried out by arginines in both cases. Arginine recognition of the major groove is also present in other T-box proteins such as TBX5.

==Structure of the DNA in the Brachyury-DNA complex==

The DNA adopted a B-like conformation with a rise of 3.3 Å, and 10.5 residues per turn (very similar to usual B-form values). The minor groove is enlarged but the DNA remains unbent: the phosphate-phosphate distances are usually 5.7 Å in the B-DNA conformation, but in this case it expands to 10 Å. However, there is no bend unlike in the binding of other transcription factors such as the TATA box binding protein.

=Functions and pathways of T protein=

The best characterised targets of the Xbra or T protein are the Xenopus embryonic fibroblast growth factor (eFGF, of which the mammalian homologue is FGF-4) and the Brachyury-induced homeobox-containing genes (Bix1, Bix2, Bix3 and Bix4).

=Known malfunctional mutations=

The Xenopus laevis homologue of Brachyury, Xbra, has a known mutation of Lys149 which destroys DNA-binding activity. This is equivalent to Asn155 and Asn353 of Eomes and VegT respectively.

TBX3

2010-07-08T12:21:40Z

Helen Ginn: Creating page

=Introduction=

TBX3 acts as a repressor and has had its crystal structure solved to 1.7 Å resolution. There are many differences between the solved structure of TBX3 and its homologue, [[Brachyury]]. Secondary structures and quaternary contacts are slightly different. TBX3 independently recognises two halves of a palindromic site whereas Brachyury is stabilised via interactions between the two monomers. Despite this, the T-box domain of TBX3 and the T-box domain of Brachyury can be superimposed with a rmsd of 1.3 Å for 167 atoms.

=Crystal structure=
{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

TBX3 expressed from residues 101 - 291 were viable proteins and were crystallised in space group P212121. These included two monomers and one DNA duplex in the asymmetric unit. The monomers themselves can be superimposed to give an rmsd of 0.5 Å. The largest differences between the TBX3 crystal structure and the T-box domain of Brachyury is between residues 173 and 184, and between strands F and G. Four residues are inserted between F and G and this adopts a 310 conformation.

=Interaction with DNA=

Loops that protrude from one end of the β barrel and the C-terminal helical extension contact both the major and minor grooves of the DNA. Strand B contains residues Arg130 and Arg131, and recognises the major groove. Arg130 is the only residue in direct contact with a DNA base in the major groove and recognises N7 and H2O.O6 of guanine (base pair 5) and the corresponding phosphate. Arg131 interacts with the DNA backbone mediated by water.

==gα3 loop interaction with DNA==

The gα3 loop spans the major groove. H3 (Tyr264, Gln265 and <scene name='User:Helen_Ginn/310c_277/3'>Asn277</scene>) form polar contacts to the DNA backbone and hydrophobic contacts to the ribose moiety. There are similar contacts in the crystal structure of Brachyury.

==310 helix interaction with DNA==

The helix 310C, also present in TBX5, contacts DNA in the minor groove and hence widens it. However, overall the DNA is not bent, as seen in other crystal structures of [[T-box proteins]]. The 310 helix interacts with DNA using <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277 (of the preceding loop), F279, K281 and F283.</scene> (See <scene name='User:Helen_Ginn/310c_277/3'>N277 only</scene>, <scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>,
<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene> and <scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>).

User:Helen Ginn

2010-07-08T12:01:26Z

Helen Ginn:

User:Helen Ginn

2010-07-08T12:00:00Z

Helen Ginn:

Undergraduate Student in Biochemistry at Oxford University.
Website: www.ribosome.co.uk

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>

<scene name='User:Helen_Ginn/310c_277/2'>N277 only</scene>

<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>

<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>

<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

User:Helen Ginn

2010-07-08T11:59:47Z

Helen Ginn: More stuff

Undergraduate Student in Biochemistry at Oxford University.
Website: www.ribosome.co.uk

=Pages to which I contribute=
[[T-box proteins]].

=Testing scenes in TBX3=

{{STRUCTURE_1h6f| PDB=1h6f | SCENE= }}

310 helix interacting with DNA with <scene name='User:Helen_Ginn/310c_277-279-281-283/1'>residues N277, F279, K281 and F283.</scene>
<scene name='User:Helen_Ginn/310c_277/2'>N277 only</scene>
<scene name='User:Helen_Ginn/310c_279/1'>F279 only</scene>
<scene name='User:Helen_Ginn/310c_281/1'>F281 only</scene>
<scene name='User:Helen_Ginn/310c_283/1'>F283 only</scene>

User:Helen Ginn

2010-07-08T11:52:19Z

Helen Ginn: Adding a test-TBX3 scene

User:Helen Ginn

2010-07-08T11:32:34Z

Helen Ginn:

TBX1

2010-07-08T08:45:56Z

Helen Ginn: adding anchor link

TBX1

2010-07-08T08:41:39Z

Helen Ginn: /* Functions and pathways of TBX1 */ minor edit

TBX1

2010-07-08T08:40:33Z

Helen Ginn: /* Insights into TBX1 */ minor edit

TBX1

2010-07-08T08:38:37Z

Helen Ginn: /* -39C → T */ Minor typo

T-box proteins

2010-07-07T08:28:02Z

Helen Ginn: Restoring references - don't know how to do them properly

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of T-box proteins are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''.

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and Tbx3 and Tbx5 on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
| Crystal structure solved
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=References=

* Current Opinion in Genetics & Development 1997, 7:474-480;
* Gene 258 (2000) 15–29;
* American Journal of Medical Genetics Part A 140A:1407–1413 (2006);
* Genome Biology 2002, 3(6):reviews3008.1–3008.7;

T-box proteins

2010-07-07T08:26:56Z

Helen Ginn: /* References */

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of T-box proteins are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''.

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and Tbx3 and Tbx5 on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
| Crystal structure solved
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=References=

<references/>

T-box proteins

2010-07-07T08:24:27Z

Helen Ginn:

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of T-box proteins are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''.

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and Tbx3 and Tbx5 on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
| Crystal structure solved
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

=References=

* Current Opinion in Genetics & Development 1997, 7:474-480;
* Gene 258 (2000) 15–29;
* American Journal of Medical Genetics Part A 140A:1407–1413 (2006);
* Genome Biology 2002, 3(6):reviews3008.1–3008.7;

TBX5

2010-07-07T08:13:12Z

Helen Ginn: TBX5 moved to 2x6u over redirect: Restoring

#REDIRECT [[2x6u]]

TBX3

2010-07-07T08:12:12Z

Helen Ginn: TBX3 moved to 1h6f over redirect: Restoring!

#REDIRECT [[1h6f]]

Brachyury

2010-07-07T08:10:56Z

Helen Ginn: Changing back from redirect page to information page

=Introduction=

Two well-known orthologues of the Homo sapiens T protein are present in mice (Brachyury) and Xenopus laevis (Xbra). The homologue of T in mice, Brachyury, was the first T-box crystal structure to be determined.

=Crystal structure=

The T-box region of the Brachyury protein was crystallised with a 24 bp palindromic DNA duplex as determined by in vitro PCR-based binding selection. It crystallised as a dimer; in one monomer residues 39-221 were visible out of a total of 226 residues, and in the other residues 39-222 were visible. Both monomers were bound to the DNA (unlike in the structure of [[TBX5]]) and interacted through a poorly conserved region of 250 Å2. The N-terminus of 38 residues and C-terminus of 4 residues were disordered in the crystal structure. Nevertheless, the crystallographic structure agrees with DNA footprinting experiments in terms of which bases are protected by the protein.

The core of the monomer is a seven-stranded β-barrel structure reminiscent of the immunoglobulin fold. Hence the T protein belongs to the superfamily of Ig-domain transcription factors. Strand D of the seven-stranded β-barrel is replaced by helix H2, and the strand-connecting regions also contain α-helices. The C-terminal amino acids are α-helical in structure, unlike TBX3 and TBX5 where they form a 310 helix. The dimer interface is mainly formed by the ends of strand C' of both proteins.

==Dimer interface==

Residues Pro125, Asp126 and Pro128 from both monomers are bridged by water molecules and the nitrogen of Asn129 forms a hydrogen-bond to Ser127 of the other subunit. To stabilise the structure a hydrophobic patch formed by Pro128, Phe130 and assisted by Met85 and Val173 exists between the two monomers. Some types of T-box proteins have exchanged amino acids for Met85 (Lys, Arg, His), Val173 (Ala) and Phe130 (Thr) which may not undergo dimer formation.

The Brachyury protein is a monomer in solution and thus only dimerises when in contact with DNA. This is supported by the fact that the contact area is only 250 Å2. Antibodies stabilise the dimer on the DNA, however the molecular mechanism of this is unknown: it is possible that the antibodies stabilise the dimer contacts when present on the DNA.

==Structural aspects of DNA binding==

The loops between the β strands make the important contacts with the DNA. 11 amino acids make polar contacts with the DNA, mainly in the minor groove. Helix H3 and H4 recognise the DNA in the minor groove, where H3 bridges the DNA backbone and is positioned by Tyr196/Asn209 contacts with the phosphates on the edges and hydrophobic contacts between guanine ribose and Ile206 in the middle. H4 points into the minor groove with hydrphobic contacts to base edges/backbone sugars and hydrogen bonds between the Phe211 carbonyl group and N2 of guanine. Note that it can be any amino acid which fills this position (i.e., not conserved), however only guanine is recognised.

It is important to note that H3/H4 is not a helix-turn-helix motif. The angle between the helices is 90° (HTH motifs: 120°) and there are 2 amino acids in the loop (HTH motifs: 4), and it interacts in the minor groove (HTH motifs interact in the major groove). The T-domain is very similar to the NF-κB p50, and superimposing these shows the major groove recognition carried out by arginines in both cases. Arginine recognition of the major groove is also present in other T-box proteins such as TBX5.

==Structure of the DNA in the Brachyury-DNA complex==

The DNA adopted a B-like conformation with a rise of 3.3 Å, and 10.5 residues per turn (very similar to usual B-form values). The minor groove is enlarged but the DNA remains unbent: the phosphate-phosphate distances are usually 5.7 Å in the B-DNA conformation, but in this case it expands to 10 Å. However, there is no bend unlike in the binding of other transcription factors such as the TATA box binding protein.

=Functions and pathways of T protein=

The best characterised targets of the Xbra or T protein are the Xenopus embryonic fibroblast growth factor (eFGF, of which the mammalian homologue is FGF-4) and the Brachyury-induced homeobox-containing genes (Bix1, Bix2, Bix3 and Bix4).

=Known malfunctional mutations=

The Xenopus laevis homologue of Brachyury, Xbra, has a known mutation of Lys149 which destroys DNA-binding activity. This is equivalent to Asn155 and Asn353 of Eomes and VegT respectively.

Brachyury

2010-07-07T08:07:42Z

Helen Ginn: Brachyury moved to 1xbr over redirect: Restoring!

#REDIRECT [[1xbr]]

Proteopedia:Table of Contents

2010-07-06T18:51:03Z

Helen Ginn: Adding TBX1

This guide to the contents of Proteopedia is maintained manually (not automatically generated) and so is inevitably incomplete. Please be sure to use the [[Help:Searching|search slots at the left]] if you don't find what you are looking for below.

<big>
{{#tree:id=siteTree|openlevels=1|close=top|open=top|

* Introduction to Structural Biology
** See [[About Macromolecular Structure]]
** Water

*** [[Water in macromolecular models|Water in Macromolecular Models]]
** Key Chemical Concepts for Structural Biology

*** [[Amino Acids]]
*** [[Cation-pi interactions]]
*** [[Hydrogen bond]]
*** [[Hydrogen in macromolecular models|Hydrogen in Macromolecular Models]]
*** [[Isoelectric point]]
*** [[Salt bridges]]

* Biomolecules
** [[About Macromolecular Structure]]

** Nucleotides, Nucleic Acids and Genetic Information
*** DNA
**** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]

** Amino Acids
*** [[Amino Acids]]
*** [[Selenocysteine]]
** Proteins, Primary Structure
*** [[Conservation, Evolutionary]]
*** [[Isoelectric point]]

** Proteins, Three-Dimensional Structure
*** [[User:Tommie_Hata/Protein_Structure_Tutorial]]
*** [[S347/The four tiers of protein structure]]
*** [[Secondary structure]]
*** Protein structural motifs
**** [[User:James D Watson/Structural Templates]]

*** Protein Misfolding
**** [[Prion protein]]
**** [[A Physical Model of the Structure of GNNQQNY from Yeast Prion Sup35]]

** Colored Proteins & those that Change Color
*** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
*** [[Dronpa]]
*** [[Factor IX]]

** DNA Binding Proteins
*** [[Helix-turn-helix motif]]
*** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

** Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies
*** Antibodies
**** [[IgA]]
**** [[Epitopes]]
**** [[Major Histocompatibility Complex Class I]]
*** [[Calmodulin in motion]]
*** [[Myoglobin]]
*** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]
*** [[Kinesin-5]]
** Lipids and Biological Membranes
** Lipid Binding Proteins
*** [[CRABP I ( Cellular Retinoic Acid Binding Protein )]]
** Membrane Transport Proteins
*** [[A Physical Model of the β2-Adrenergic Receptor]]
*** [[Lactose Permease]]
*** [[Proton Channels]]
*** [[Ion channels]]
**** [[M2 Proton Channel]]
**** [[Voltage-gated calcium channels]]
*** [[Mechanosensitive channels: opening and closing]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]

** Prions and Intrinsically Disordered Proteins
*** [[Prion protein]]
*** [[Doppel]]
*** [[Intrinsically Disordered Protein]]

** Toxins
*** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

** Mitosis, Meiosis and Cargo Transport Proteins
*** [[Kinesin-5]]

** Viruses
*** [[User:Wayne Decatur/Suppression of RNA Silencing by Viruses]]
*** Filamentous bacteriophage
**** [[G3p]] - minor coat protein found on the surface of filamentous bacteriophage
*** HIV
**** [[HIV-1 protease]]
**** [[HIV-1 Gag]]
**** [[HIV-1 Gag Recruitment of Tsg101 and the Viral Budding Process]]
**** [[User:Eric Martz/Molecular Playground/HIVDrug]]
*** Herpes Simplex Virus
**** [[Herpes Simplex Virus Thymidine Kinase]]
*** Influenza
**** [[Influenza hemagglutinin]]
**** [[Avian Influenza Neuraminidase, Tamiflu and Relenza]]

* Colored Proteins & those that Change Color
** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
** [[Dronpa]]
** [[Factor IX]]

* DNA Binding Proteins
** [[Helix-turn-helix motif]]
** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

* Enzymes
** Enzymatic Catalysis
*** Acid-beta-glucosidase
**** reHuman Acid-beta-glucosidase made in CHO cells [[1ogs]]
**** reHuman Acid-beta-glucosidase made in CHO cells bound to conduritol B epoxide [[1y7v]]
**** reHuman Acid-beta-glucosidase made in carrot cells complexed with N-butyl-deoxynojirimycin [[2v3d]]
**** Velaglucerase Alfa [[2wkl]]
*** Acid Proteases
**** [[HIV-1 protease]]

**** [[Streptomyces griseus Aminopeptidase (SGAP)]]; [[Aminopeptidase]]
*** [[Aconitase]]
*** Cysteine Proteases
*** [[Hen Egg-White (HEW) Lysozyme]]
*** [[Choline Oxidase]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Metalloproteases]]
**** [[Matrix metalloproteinases]]
*** Oxidoreductases
**** [[NADH quinone oxidoreductase ]]
*** [[Phosphofructokinase %28PFK%29]]
*** [[Pyruvate phosphate dikinase]]
*** [[Serotonin N-acetyltransferase]]
*** Serine Hydrolases
**** [[Acetylcholinesterase]] (AChE)
***** [[Acetylcholine]]
***** [[Flexibility of aromatic residues in acetylcholinesterase]]
***** [[AChE inhibitors and substrates]]
****** [[1eve]] AChE-Aricept complex; [[1eve (Arabic)]]; [[1eve (Chinese)]]; [[1eve (Italian)]]; [[1eve (Russian)]]; [[1eve (Spanish)]]; [[1eve (Turkish)]]
****** [[AChE bivalent inhibitors]]
**** [[Tobacco Etch Virus (TEV) Protease]]
*** [[Serine Protease]]
**** [[Trypsin]]
*** [[Triose Phosphate Isomerase]]
** Enzyme Inhibitors
*** [[Alpha-1-antitrypsin]]
** Enzyme Kinetics, Inhibition, and Control
***[[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
** Biochemical Signaling
*** [[Nitric oxide synthase]], [[NOS structures]]
*** [[Recoverin, a calcium-activated myristoyl switch]]
*** [[Bcl-2]]
*** [[C-Myc]]
*** [[C-di-GMP signaling]]

** Enzymes - Molecular Machines
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Pyruvate phosphate dikinase]]

* Fibrous Proteins
** [[Coiled coil]]
** [[Collagen]]

* Membrane Transport Proteins
** [[A Physical Model of the β2-Adrenergic Receptor]]
** [[Lactose Permease]]
** [[Proton Channels]]
** [[Ion channels]]
*** [[M2 Proton Channel]]
*** [[Voltage-gated calcium channels]]
** [[Mechanosensitive channels: opening and closing]]
** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]

* Myoglobin & Hemoglobin
** [[Myoglobin]]
** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]

* Nervous System Proteins

** [[Acetylcholinesterase]] (AChE)
*** [[Acetylcholine]]
*** [[Flexibility of aromatic residues in acetylcholinesterase]]

*** AChE inhibitors (In Different Languages)
**** [[1eve]] AChE-Aricept complex, [[1eve (Arabic)]], [[1eve (Chinese)]], [[1eve (Italian)]], [[1eve (Russian)]], [[1eve (Spanish)]], [[1eve (Turkish)]]
**** [[1vot]] AChE-Huperzine A complex, [[1vot (Chinese)]]

*** Acetylcholinesterase - AChE native
**** [[3lii]] – hAChE - recombinant human
**** [[1ea5]], [[2ace]] – ''Tc''AChE – trigonal – ''Torpedo californica''
**** [[2j3d]] – ''Tc''AChE – monoclinic
**** [[1w75]] – ''Tc''AChE – orthorhombic
**** [[1eea]] – ''Tc''AChE – cubic
**** [[2vt6]], [[2vt7]] – ''Tc''AChE – different dosage
**** [[1qid]] to [[1qim]] - ''Tc''AChE synchrotron radiation damage
**** [[1j06]], [[1maa]] – mAChE - mouse
**** [[1qo9]] – ''Dm''AChE - ''Drosophila''
**** [[1c2o]], [[1c2b]] – electrophorus AChE – Electric eel

*** AChE active site inhibitors conjugating at the bottom of the active site gorge
**** [[2w9i]] – ''Tc''AChE + methylene blue
**** [[2wls]] – MosAChE + AMTS13
**** [[2vq6]] – ''Tc''AChE + 2-PAM
**** [[2j3q]] – ''Tc''AChE + Thioflavin T
**** [[2ha0]] – mAChE + ketoamyltrimethylammonium
**** [[2h9y]] – mAChE + TMTFA
**** [[1gpk]], [[1gpn]], [[1vot]] – ''Tc''AChE + huperzine
**** [[1gqr]] – ''Tc''AChE + rivastigmine
**** [[1gqs]] – ''Tc''AChE + NAP
**** [[1e66]] – ''Tc''AChE + huprine
**** [[1dx4]], [[1qon]] – ''Dm''AChE + tacrine derivative
**** [[1oce]] – ''Tc''AChE + MF268
**** [[1ax9]], [[1ack]] – ''Tc''AChE + edrophonium
**** [[1amn]] – ''Tc''AChE + TMTFA
**** [[1acj]] – ''Tc''AChE + tacrine

*** AChE peripheral site inhibitors conjugating at the surface of the protein
**** [[1ku6]] - mAChE + fasciculin 2
**** [[1ku6]], [[1mah]] - mAChE + fasciculin 2
**** [[1j07]] - mAChE + decidium
**** [[1n5m]] - mAChE + gallamine
**** [[1n5r]] - mAChE + propidium
**** [[1b41]], [[1f8u]] - hAChE + fasciculin 2
**** [[1fss]] - TcAChE + fasciculin 2

*** AChE bis inhibitors spanning the active site gorge
**** [[AChE bivalent inhibitors]]
**** [[3i6m]] – ''Tc''AChE + N-piperidinopropyl galanthamine
**** [[3i6z]] - ''Tc''AChE + saccharinohexyl galanthamine
**** [[1zgb]], [[1zgc]] – ''Tc''AChE + tacrine (10) hupyridone
**** [[2w6c]] – ''Tc''AChE + bis-(-)-nor-meptazinol
**** [[2ckm]], [[2cmf]] – ''Tc''AChE + bis-tacrine
**** [[2cek]] – ''Tc''AChE + N-[8-(1,2,3,4-tetrahydroacridin-9-ylthio)octyl]-1,2,3,4-tetrahydroacridin-9-amine
**** [[1ut6]] - ''Tc''AChE + N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1odc]] - ''Tc''AChE + N-4-quinolyl-N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1w4l]], [[1w6r]], [[1w76]], [[1dx6]], [[1qti]] - TcAChE + galanthamine and derivative
**** [[1q83]], [[1q84]] - mAChE + TZ2PA6
**** [[1h22]], [[1h23]] – ''Tc''AChE + bis-hupyridone
**** [[1hbj]] – ''Tc''AChE + quinoline derivativev
**** [[1e3q]] – ''Tc''AChE + bw284c51
**** [[1eve]] – ''Tc''AChE + e2020
**** [[1acl]] – ''Tc''AChE + decamethonium

*** AChE organophosphate inhibitors causing irreversible inhibition
**** [[2wu3]] – mAChE + fenamiphos and HI-6
**** [[2wu4]] – mAChE + fenamiphos and ortho-7
**** [[2jgf]] - mAChE + fenamiphos
**** [[2wfz]], [[2wg0]], [[1som]] - ''Tc''AChE + soman
**** [[2wg1]] - ''Tc''AChE + soman + 2-PAM
**** [[2whp]], [[2whq]], [[2whr]] – mAChE + sarin and HI-6
**** [[2jgg]] - mAChE + sarin
**** [[2jgl]] - mAChE + VX and sarin
**** [[1cfj]] - ''Tc''AChE + sarin, GB
**** [[3dl4]], [[3dl7]] – mAChE + tabun
**** [[2jey]] – mAChE + HLO-7
**** [[2c0p]], [[2c0q]] - mAChE + tabun
**** [[2jez]] - mAChE + tabun + HLO-7
**** [[2jf0]] - mAChE + tabun + Ortho-7
**** [[2jgh]] - mAChE + VX
**** [[1vxo]], [[1vxr]] - ''Tc''AChE + VX
**** [[2jgi]], [[2jgm]] - mAChE + DFP
**** [[1dfp]] - ''Tc''AChE + DFP
**** [[2jgj]], [[2jgk]], [[2jge]] - mAChE + methamidophos
**** [[2gyu]] - mAChE + HI-6
**** [[2gyv]] - mAChE + Ortho-7
**** [[2gyw]] - mAChE + obidoxime

*** AChE substrate analogues mimicking the binding of the substrate acetylcholine
**** [[2ha4]] – mAChE (mutant) + acetylcholine
**** [[2vja]], [[2vjb]], [[2vjc]], [[2vjd]], [[2cf5]] – ''Tc''AChE + 4-oxo-N,N,N-trimethylpentanaminium
**** [[2v96]], [[2v97]], [[2v98]], [[2v99]] – ''Tc''AChE + 1-(2-nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine
**** [[2ha2]] – mAChE + succinylcholine
**** [[2ha3]] - mAChE + choline
**** [[2ha5]] – mAChE (mutant) + acetylthiocholine
**** [[2ha6]] – mAChE (mutant) + succinylthiocholine
**** [[2ha7]] – mAChE (mutant) + butyrylthiocholine
**** [[2ch4]], [[2c58]] – ''Tc''AChE + acetylthiocholine
**** [[2c5g]] – ''Tc''AChE + thiocholine

*** Others…
**** [[2j4f]] – ''Tc''AChE + Hg
**** [[1vzj]] – ''Tc''AChE tetramerization domain
**** [[1jjb]] – ''Tc''AChE + PEG

** [[Acetylcholine binding protein]] (AChBP)
** [[Butyrylcholinesterase]] (BChE)

* Prions and Intrinsically Disordered Proteins
** [[Prion protein]]
** [[Doppel]]
** [[Intrinsically Disordered Protein]]

* Small Iron Sulfur Proteins
** [[Ferredoxin]] (Fd)
*** 2Fe-2S containing ferredoxins
**** [[3hui]] – Fd – ''Rhodopseudomonas palustris''
**** [[2kaj]], [[1dox]], [[1doy]] – SyFd +Ga – Synechocystis – NMR
**** [[1off]] – SyFd
**** [[3gce]] – Fd – Nocardioides aromaticivorans
**** [[2e4p]], [[2e4q]] - Fd – ''Pseudomonas sp.''
**** [[2q3w]], [[1vm9]] - PmFd (mutant) – ''Pseudomonas mendocina''
**** [[2i7f]] - Fd – ''Rhodobacter capsulatus''
**** [[1rfk]] - Fd – Cyanobacterium ''masticogladus laminosus''
**** [[1vck]] - Fd – ''Pseudomonas resinovorans''
**** [[1wri]], [[1frr]] - Fd – Equisetum arvense
**** [[1sjg]] - PmFd– NMR
**** [[1iue]] - Fd– Plasmodium falciparum
**** [[1m2a]] –AeFd – Aquifex aeolicus
**** [[1m2b]], [[1m2d]], [[1f37]], [[1f5b]], [[1f5c]] – AeFd (mutant)
**** [[1l5p]] – Fd – Trichomonas vaginalis
**** [[1i7h]] - Fd – Escherichia coli
**** [[1czp]], [[1qt9]], [[1frd]], [[1fxa]] - aFd– anabaena
**** [[1j7a]], [[1j7b]], [[1j7c]] , [[1qoa]], [[1qob]], [[1qof]], [[1qog]]- aFd (mutant)
**** [[1e0z]] – Fd – Halobacterium salinarium
**** [[1pfd]] – Fd – Petroselinum crispum – NMR
**** [[1a70]] - Fd (mutant) – Spinacia oleracea
**** [[1awd]] - Fd – Chlorella fusca
**** [[2cjn]], [[2cjo]], [[1roe]] – SyFd – NMR
**** [[1rof]] – SyFd – Synechococcus elongates
**** [[1doi]] - Fd – Haloarcula marismortui
**** [[4fxc]] – Fd – Spirulina platensis
**** [[1fxi]] – Fd – Aphanothece sacrum
**** [[3dqy]], [[2qpz]] - Fd – Pseudomonas putida

*** 4Fe-4S containing ferredoxins

**** [[3eun]] – AvFd – Allochromatium vinosum
**** [[3exy]] - AvFd (mutant)
**** [[2vkr]] - Fd+Zn – Acidianus ambivalens
**** [[2z8q]] - PfFd (mutant) – Pyrococcus furiosus
**** [[2fgo]] - Fd– Pseudomonas aeruginosa
**** [[1iqz]], [[1ir0]] - BtFd – Bacillus thermoproteolyticus
**** [[1rgv]] - Fd – Thauera aromatica
**** [[1dax]], [[1dfd]] – DaFd – Desulfovibrio africanus – NMR
**** [[1fxr]] - DaFd
**** [[1vjw]] – Fd – Thermotoga maritima

*** 3Fe-4S containing ferredoxins

**** [[2v2k]] – Fd – Mycobacterium smegmatis
**** [[1wtf]] - BtFd (mutant)
**** [[1sj1]] - PfFd
**** [[1fxd]] - DgFd – Desulfovibrio gigas
**** [[1f2g]] – DgFd – NMR
**** [[1xer]] - Fd – Sulfolobus tokodaii

*** 4Fe-4S+3Fe-4S containing ferredoxins

**** [[1gao]], [[6fdr]], [[7fd1]], [[7fdr]], [[1axq]], [[6fd1]], [[1frh]], **** [[1fri]],[[1frj]], [[1frk]], [[1frl]], [[1frm]], [[1fda]], [[1fdb]], **** [[1fdd]], [[5fd1]], [[1fer]] – AvFd – Azotobacter vinelandii
**** [[1pc4]], [[1pc5]], [[1g6b]], [[1g3o]], [[1ff2]], [[1b0v]], [[1d3w]], **** [[1b0t]], [[1a6l]], [[1ftc]], [[1frx]], [[2fd2]], [[1fd2]] - AvFd (mutant)
**** [[1h98]] – Fd – Thermus thermophilus
**** [[1a8p]], [[1bd6]] - BsFd – Bacillus schlegelii – NMR

*** 4Fe-4S+4Fe-4S containing ferredoxins

**** [[1dur]] – Fd – Peptoniphilus asaccarolyticus
**** [[1bwe]], [[1bqx]] - BsFd (mutant) – NMR
**** [[2fdn]], [[1fca]] , [[1fdn]]- Fd – Clostridium acidi-urici
**** [[1blu]] - Fd – Chromatium vinosum
**** [[1clf ]]– Fd – Clostridium pasteurianum – NMR

*** Adrenoredoxin

**** [[2jqr]] – ADR Fd domain (mutant)+cytochrome c (mutant) – yeast – NMR
**** [[2bt6]] – cADR1 modified – cow
**** [[1l6u]], [[1l6v]] – cADR1 – NMR
**** [[1e6e]] – cADR (mutant)+ADR reductase
**** [[1cje]], [[1ayf]] - cADR

*** Putidaredoxin

**** [[1yji]], [[1yjj]], [[1pdx]] – PpPUT – Pseudomonas putida – NMR
**** [[3lb8]] – PpPUT (mutant)+PUT reductase
**** [[1xln]], [[1xlo]], [[1xlp]], [[1xlq]], [[1r7s]], [[1oqq]], [[1oqr]] - PpPUT (mutant)
**** [[1gpx]], [[1put]]- PpPUT (mutant) - NMR

*** Terpredoxin

**** [[1b9r]] – TER – Pseudomonas - NMR

* Toxins
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]
** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

* Diseases
** Cancer
*** [[SRC]]
*** [[Proteins involved in cancer]]

* Evolution
** [[Conservation, Evolutionary]]
** [[Extremophiles]]

* Gene Expression and Replication
** Nucleic Acid Structure
*** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]
*** [[Nucleosomes]]

** DNA Replication, Repair, and Recombination
*** [[DNA Replication,Transcription and Translation]]
*** [[DNA Polymerase I]]
*** [[PcrA helicase]]
*** [[Fpg Nei Protein Superfamily]] - DNA Repair and Base Excision DNA Repair
*** [[Human RecQ-Like protein 1]] - RecQ family of DNA helicases are conserved in from bacteria to man
*** [[Structure of E. coli DnaC helicase loader]]
*** [[1x9n#Crystal Structure of Human DNA Ligase I bound to 5.27-adenylated.2C nicked DNA]]
*** [[Rop protein]]

** Transcription and RNA Processing
*** T-box family
**** [[T-box proteins]]
**** [[Brachyury]]
**** [[TBX1]]
**** [[TBX15]]
*** [[C-Myc]]
*** [[Lac repressor]]
*** [[Reverse transcriptase]]
*** [[TATA-Binding Protein]]
*** [[RSP1275]]
*** [[Transcription Termination Factor Rho]]

** Protein Synthesis
*** [[Ribosome]]
*** [[Large Ribosomal Subunit of Haloarcula|Large Ribosomal Subunit]]
*** [[SelB Recognition]]
** Regulation of Gene Expression
*** [[Lac repressor]]
*** [[Irr]] (Iron Response Regulator )
*** Oncogenes
**** [[P53]]
**** [[SRC]]
*** [[Tangible Models of Cdc42 Interacting With Intersectin]]

* Immune System
** Antibodies
*** [[IgA]]
*** [[Epitopes]]
** [[Major Histocompatibility Complex Class I]]
*** [[Human beta two microglobulin]]

* Metabolism
** Introduction to Metabolism

** Glucose Catabolism
*** [[Triose Phosphate Isomerase]]
***[[Phosphofructokinase %28PFK%29]]

** Glycogen Metabolism and Gluconeogenesis
*** [[Phosphoglucose isomerase]]
*** [[Calmodulin in motion]]
*** [[Biotin Protein Ligase]]

** Citric Acid Cycle
*** [[Aconitase]]

** Electron Transport and Oxidative Phosphorylation
*** [[NADH quinone oxidoreductase ]]

** Photosynthesis
*** [[Photosystem II]]
*** [[Ribulose-1,5-bisphosphate carboxylase/oxygenase]]
*** [[PrrA in Rhodobacter sphaeroides]]
*** [[Pyruvate phosphate dikinase]]

** Lipid Metabolism
*** [[Acid-beta-glucosidase]]
** Amino Acid Metabolism
*** [[Aromatic amino acid hydroxylases]]
*** [[Phenylalanine hydroxylase]]
*** [[Tyrosine hydroxylase]]
*** [[ATP Phosphoribosyl Transferase]]
*** [[Isochorismate pyruvate lyase]]
** Mammalian Fuel Metabolism: Integration and Regulation
** Nucleotide Metabolism
*** [[Dihydrofolate reductase]]

* Methods of Structure Determination
** X-ray
*** [[X-ray crystallography]]
**** [[Asymmetric Unit]]
**** [[Biological Unit]]
**** [[Electron density maps]]
*** SAXS
** NMR
*** [[NMR Ensembles of Models]]
** Electron Microscopy

* Methods of Structure & Sequence Analysis
** Structural Analysis & Visualization
*** [[CPK]] - Corey-Pauling-Koltun spacefilling molecular models and color scheme for elements
*** [[Chime]]
*** Jmol
**** [[S347/Visualising protein structure|Visualising Protein Structure]] - Introduction to Jmol
**** [[FirstGlance in Jmol]]
*** [[User:Wayne Decatur/Teaching Proteopedia|Teaching Proteopedia]]
*** [[User:Wayne Decatur/Generate Unfolded Structures|Generate Unfolded Structures]]
*** Homology Model
**** [[User:Wayne Decatur/Homology Modeling|Homology Modeling]]
**** [[User:Emi Nakayama/TRIM5a Homology Models|TRIM5a Homology Models]] - Differences in models as a function of their templates
*** [[DRuMS]] - set of standard color schemes for macromolecular visualization

** Sequence Analysis
*** [[User:Wayne Decatur/Sequence analysis tools|Sequence Analysis Tools]]

* Model Structures
** See [[Theoretical models]]
** [[African Malaria Mosquito Acetylcholinesterase]]
** [[Structure of E. coli DnaC helicase loader]]
** [[User:Yuan-Ping Pang/HAB•BoNTAe]]

* Miscellaneous
** [[Molecular Playground]]
** [[Research Groups]]
}}
</big>

TBX1

2010-07-06T18:50:04Z

Helen Ginn: New page

Proteopedia:Table of Contents

2010-07-06T18:42:22Z

Helen Ginn: Changing T to Brachyury

This guide to the contents of Proteopedia is maintained manually (not automatically generated) and so is inevitably incomplete. Please be sure to use the [[Help:Searching|search slots at the left]] if you don't find what you are looking for below.

<big>
{{#tree:id=siteTree|openlevels=1|close=top|open=top|

* Introduction to Structural Biology
** See [[About Macromolecular Structure]]
** Water

*** [[Water in macromolecular models|Water in Macromolecular Models]]
** Key Chemical Concepts for Structural Biology

*** [[Amino Acids]]
*** [[Cation-pi interactions]]
*** [[Hydrogen bond]]
*** [[Hydrogen in macromolecular models|Hydrogen in Macromolecular Models]]
*** [[Isoelectric point]]
*** [[Salt bridges]]

* Biomolecules
** [[About Macromolecular Structure]]

** Nucleotides, Nucleic Acids and Genetic Information
*** DNA
**** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]

** Amino Acids
*** [[Amino Acids]]
*** [[Selenocysteine]]
** Proteins, Primary Structure
*** [[Conservation, Evolutionary]]
*** [[Isoelectric point]]

** Proteins, Three-Dimensional Structure
*** [[User:Tommie_Hata/Protein_Structure_Tutorial]]
*** [[S347/The four tiers of protein structure]]
*** [[Secondary structure]]
*** Protein structural motifs
**** [[User:James D Watson/Structural Templates]]

*** Protein Misfolding
**** [[Prion protein]]
**** [[A Physical Model of the Structure of GNNQQNY from Yeast Prion Sup35]]

** Colored Proteins & those that Change Color
*** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
*** [[Dronpa]]
*** [[Factor IX]]

** DNA Binding Proteins
*** [[Helix-turn-helix motif]]
*** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

** Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies
*** Antibodies
**** [[IgA]]
**** [[Epitopes]]
**** [[Major Histocompatibility Complex Class I]]
*** [[Calmodulin in motion]]
*** [[Myoglobin]]
*** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]
*** [[Kinesin-5]]
** Lipids and Biological Membranes
** Lipid Binding Proteins
*** [[CRABP I ( Cellular Retinoic Acid Binding Protein )]]
** Membrane Transport Proteins
*** [[A Physical Model of the β2-Adrenergic Receptor]]
*** [[Lactose Permease]]
*** [[Proton Channels]]
*** [[Ion channels]]
**** [[M2 Proton Channel]]
**** [[Voltage-gated calcium channels]]
*** [[Mechanosensitive channels: opening and closing]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]

** Prions and Intrinsically Disordered Proteins
*** [[Prion protein]]
*** [[Doppel]]
*** [[Intrinsically Disordered Protein]]

** Toxins
*** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

** Mitosis, Meiosis and Cargo Transport Proteins
*** [[Kinesin-5]]

** Viruses
*** [[User:Wayne Decatur/Suppression of RNA Silencing by Viruses]]
*** Filamentous bacteriophage
**** [[G3p]] - minor coat protein found on the surface of filamentous bacteriophage
*** HIV
**** [[HIV-1 protease]]
**** [[HIV-1 Gag]]
**** [[HIV-1 Gag Recruitment of Tsg101 and the Viral Budding Process]]
**** [[User:Eric Martz/Molecular Playground/HIVDrug]]
*** Herpes Simplex Virus
**** [[Herpes Simplex Virus Thymidine Kinase]]
*** Influenza
**** [[Influenza hemagglutinin]]
**** [[Avian Influenza Neuraminidase, Tamiflu and Relenza]]

* Colored Proteins & those that Change Color
** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
** [[Dronpa]]
** [[Factor IX]]

* DNA Binding Proteins
** [[Helix-turn-helix motif]]
** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

* Enzymes
** Enzymatic Catalysis
*** Acid-beta-glucosidase
**** reHuman Acid-beta-glucosidase made in CHO cells [[1ogs]]
**** reHuman Acid-beta-glucosidase made in CHO cells bound to conduritol B epoxide [[1y7v]]
**** reHuman Acid-beta-glucosidase made in carrot cells complexed with N-butyl-deoxynojirimycin [[2v3d]]
**** Velaglucerase Alfa [[2wkl]]
*** Acid Proteases
**** [[HIV-1 protease]]

**** [[Streptomyces griseus Aminopeptidase (SGAP)]]; [[Aminopeptidase]]
*** [[Aconitase]]
*** Cysteine Proteases
*** [[Hen Egg-White (HEW) Lysozyme]]
*** [[Choline Oxidase]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Metalloproteases]]
**** [[Matrix metalloproteinases]]
*** Oxidoreductases
**** [[NADH quinone oxidoreductase ]]
*** [[Phosphofructokinase %28PFK%29]]
*** [[Pyruvate phosphate dikinase]]
*** [[Serotonin N-acetyltransferase]]
*** Serine Hydrolases
**** [[Acetylcholinesterase]] (AChE)
***** [[Acetylcholine]]
***** [[Flexibility of aromatic residues in acetylcholinesterase]]
***** [[AChE inhibitors and substrates]]
****** [[1eve]] AChE-Aricept complex; [[1eve (Arabic)]]; [[1eve (Chinese)]]; [[1eve (Italian)]]; [[1eve (Russian)]]; [[1eve (Spanish)]]; [[1eve (Turkish)]]
****** [[AChE bivalent inhibitors]]
**** [[Tobacco Etch Virus (TEV) Protease]]
*** [[Serine Protease]]
**** [[Trypsin]]
*** [[Triose Phosphate Isomerase]]
** Enzyme Inhibitors
*** [[Alpha-1-antitrypsin]]
** Enzyme Kinetics, Inhibition, and Control
***[[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
** Biochemical Signaling
*** [[Nitric oxide synthase]], [[NOS structures]]
*** [[Recoverin, a calcium-activated myristoyl switch]]
*** [[Bcl-2]]
*** [[C-Myc]]
*** [[C-di-GMP signaling]]

** Enzymes - Molecular Machines
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Pyruvate phosphate dikinase]]

* Fibrous Proteins
** [[Coiled coil]]
** [[Collagen]]

* Membrane Transport Proteins
** [[A Physical Model of the β2-Adrenergic Receptor]]
** [[Lactose Permease]]
** [[Proton Channels]]
** [[Ion channels]]
*** [[M2 Proton Channel]]
*** [[Voltage-gated calcium channels]]
** [[Mechanosensitive channels: opening and closing]]
** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]

* Myoglobin & Hemoglobin
** [[Myoglobin]]
** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]

* Nervous System Proteins

** [[Acetylcholinesterase]] (AChE)
*** [[Acetylcholine]]
*** [[Flexibility of aromatic residues in acetylcholinesterase]]

*** AChE inhibitors (In Different Languages)
**** [[1eve]] AChE-Aricept complex, [[1eve (Arabic)]], [[1eve (Chinese)]], [[1eve (Italian)]], [[1eve (Russian)]], [[1eve (Spanish)]], [[1eve (Turkish)]]
**** [[1vot]] AChE-Huperzine A complex, [[1vot (Chinese)]]

*** Acetylcholinesterase - AChE native
**** [[3lii]] – hAChE - recombinant human
**** [[1ea5]], [[2ace]] – ''Tc''AChE – trigonal – ''Torpedo californica''
**** [[2j3d]] – ''Tc''AChE – monoclinic
**** [[1w75]] – ''Tc''AChE – orthorhombic
**** [[1eea]] – ''Tc''AChE – cubic
**** [[2vt6]], [[2vt7]] – ''Tc''AChE – different dosage
**** [[1qid]] to [[1qim]] - ''Tc''AChE synchrotron radiation damage
**** [[1j06]], [[1maa]] – mAChE - mouse
**** [[1qo9]] – ''Dm''AChE - ''Drosophila''
**** [[1c2o]], [[1c2b]] – electrophorus AChE – Electric eel

*** AChE active site inhibitors conjugating at the bottom of the active site gorge
**** [[2w9i]] – ''Tc''AChE + methylene blue
**** [[2wls]] – MosAChE + AMTS13
**** [[2vq6]] – ''Tc''AChE + 2-PAM
**** [[2j3q]] – ''Tc''AChE + Thioflavin T
**** [[2ha0]] – mAChE + ketoamyltrimethylammonium
**** [[2h9y]] – mAChE + TMTFA
**** [[1gpk]], [[1gpn]], [[1vot]] – ''Tc''AChE + huperzine
**** [[1gqr]] – ''Tc''AChE + rivastigmine
**** [[1gqs]] – ''Tc''AChE + NAP
**** [[1e66]] – ''Tc''AChE + huprine
**** [[1dx4]], [[1qon]] – ''Dm''AChE + tacrine derivative
**** [[1oce]] – ''Tc''AChE + MF268
**** [[1ax9]], [[1ack]] – ''Tc''AChE + edrophonium
**** [[1amn]] – ''Tc''AChE + TMTFA
**** [[1acj]] – ''Tc''AChE + tacrine

*** AChE peripheral site inhibitors conjugating at the surface of the protein
**** [[1ku6]] - mAChE + fasciculin 2
**** [[1ku6]], [[1mah]] - mAChE + fasciculin 2
**** [[1j07]] - mAChE + decidium
**** [[1n5m]] - mAChE + gallamine
**** [[1n5r]] - mAChE + propidium
**** [[1b41]], [[1f8u]] - hAChE + fasciculin 2
**** [[1fss]] - TcAChE + fasciculin 2

*** AChE bis inhibitors spanning the active site gorge
**** [[AChE bivalent inhibitors]]
**** [[3i6m]] – ''Tc''AChE + N-piperidinopropyl galanthamine
**** [[3i6z]] - ''Tc''AChE + saccharinohexyl galanthamine
**** [[1zgb]], [[1zgc]] – ''Tc''AChE + tacrine (10) hupyridone
**** [[2w6c]] – ''Tc''AChE + bis-(-)-nor-meptazinol
**** [[2ckm]], [[2cmf]] – ''Tc''AChE + bis-tacrine
**** [[2cek]] – ''Tc''AChE + N-[8-(1,2,3,4-tetrahydroacridin-9-ylthio)octyl]-1,2,3,4-tetrahydroacridin-9-amine
**** [[1ut6]] - ''Tc''AChE + N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1odc]] - ''Tc''AChE + N-4-quinolyl-N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1w4l]], [[1w6r]], [[1w76]], [[1dx6]], [[1qti]] - TcAChE + galanthamine and derivative
**** [[1q83]], [[1q84]] - mAChE + TZ2PA6
**** [[1h22]], [[1h23]] – ''Tc''AChE + bis-hupyridone
**** [[1hbj]] – ''Tc''AChE + quinoline derivativev
**** [[1e3q]] – ''Tc''AChE + bw284c51
**** [[1eve]] – ''Tc''AChE + e2020
**** [[1acl]] – ''Tc''AChE + decamethonium

*** AChE organophosphate inhibitors causing irreversible inhibition
**** [[2wu3]] – mAChE + fenamiphos and HI-6
**** [[2wu4]] – mAChE + fenamiphos and ortho-7
**** [[2jgf]] - mAChE + fenamiphos
**** [[2wfz]], [[2wg0]], [[1som]] - ''Tc''AChE + soman
**** [[2wg1]] - ''Tc''AChE + soman + 2-PAM
**** [[2whp]], [[2whq]], [[2whr]] – mAChE + sarin and HI-6
**** [[2jgg]] - mAChE + sarin
**** [[2jgl]] - mAChE + VX and sarin
**** [[1cfj]] - ''Tc''AChE + sarin, GB
**** [[3dl4]], [[3dl7]] – mAChE + tabun
**** [[2jey]] – mAChE + HLO-7
**** [[2c0p]], [[2c0q]] - mAChE + tabun
**** [[2jez]] - mAChE + tabun + HLO-7
**** [[2jf0]] - mAChE + tabun + Ortho-7
**** [[2jgh]] - mAChE + VX
**** [[1vxo]], [[1vxr]] - ''Tc''AChE + VX
**** [[2jgi]], [[2jgm]] - mAChE + DFP
**** [[1dfp]] - ''Tc''AChE + DFP
**** [[2jgj]], [[2jgk]], [[2jge]] - mAChE + methamidophos
**** [[2gyu]] - mAChE + HI-6
**** [[2gyv]] - mAChE + Ortho-7
**** [[2gyw]] - mAChE + obidoxime

*** AChE substrate analogues mimicking the binding of the substrate acetylcholine
**** [[2ha4]] – mAChE (mutant) + acetylcholine
**** [[2vja]], [[2vjb]], [[2vjc]], [[2vjd]], [[2cf5]] – ''Tc''AChE + 4-oxo-N,N,N-trimethylpentanaminium
**** [[2v96]], [[2v97]], [[2v98]], [[2v99]] – ''Tc''AChE + 1-(2-nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine
**** [[2ha2]] – mAChE + succinylcholine
**** [[2ha3]] - mAChE + choline
**** [[2ha5]] – mAChE (mutant) + acetylthiocholine
**** [[2ha6]] – mAChE (mutant) + succinylthiocholine
**** [[2ha7]] – mAChE (mutant) + butyrylthiocholine
**** [[2ch4]], [[2c58]] – ''Tc''AChE + acetylthiocholine
**** [[2c5g]] – ''Tc''AChE + thiocholine

*** Others…
**** [[2j4f]] – ''Tc''AChE + Hg
**** [[1vzj]] – ''Tc''AChE tetramerization domain
**** [[1jjb]] – ''Tc''AChE + PEG

** [[Acetylcholine binding protein]] (AChBP)
** [[Butyrylcholinesterase]] (BChE)

* Prions and Intrinsically Disordered Proteins
** [[Prion protein]]
** [[Doppel]]
** [[Intrinsically Disordered Protein]]

* Small Iron Sulfur Proteins
** [[Ferredoxin]] (Fd)
*** 2Fe-2S containing ferredoxins
**** [[3hui]] – Fd – ''Rhodopseudomonas palustris''
**** [[2kaj]], [[1dox]], [[1doy]] – SyFd +Ga – Synechocystis – NMR
**** [[1off]] – SyFd
**** [[3gce]] – Fd – Nocardioides aromaticivorans
**** [[2e4p]], [[2e4q]] - Fd – ''Pseudomonas sp.''
**** [[2q3w]], [[1vm9]] - PmFd (mutant) – ''Pseudomonas mendocina''
**** [[2i7f]] - Fd – ''Rhodobacter capsulatus''
**** [[1rfk]] - Fd – Cyanobacterium ''masticogladus laminosus''
**** [[1vck]] - Fd – ''Pseudomonas resinovorans''
**** [[1wri]], [[1frr]] - Fd – Equisetum arvense
**** [[1sjg]] - PmFd– NMR
**** [[1iue]] - Fd– Plasmodium falciparum
**** [[1m2a]] –AeFd – Aquifex aeolicus
**** [[1m2b]], [[1m2d]], [[1f37]], [[1f5b]], [[1f5c]] – AeFd (mutant)
**** [[1l5p]] – Fd – Trichomonas vaginalis
**** [[1i7h]] - Fd – Escherichia coli
**** [[1czp]], [[1qt9]], [[1frd]], [[1fxa]] - aFd– anabaena
**** [[1j7a]], [[1j7b]], [[1j7c]] , [[1qoa]], [[1qob]], [[1qof]], [[1qog]]- aFd (mutant)
**** [[1e0z]] – Fd – Halobacterium salinarium
**** [[1pfd]] – Fd – Petroselinum crispum – NMR
**** [[1a70]] - Fd (mutant) – Spinacia oleracea
**** [[1awd]] - Fd – Chlorella fusca
**** [[2cjn]], [[2cjo]], [[1roe]] – SyFd – NMR
**** [[1rof]] – SyFd – Synechococcus elongates
**** [[1doi]] - Fd – Haloarcula marismortui
**** [[4fxc]] – Fd – Spirulina platensis
**** [[1fxi]] – Fd – Aphanothece sacrum
**** [[3dqy]], [[2qpz]] - Fd – Pseudomonas putida

*** 4Fe-4S containing ferredoxins

**** [[3eun]] – AvFd – Allochromatium vinosum
**** [[3exy]] - AvFd (mutant)
**** [[2vkr]] - Fd+Zn – Acidianus ambivalens
**** [[2z8q]] - PfFd (mutant) – Pyrococcus furiosus
**** [[2fgo]] - Fd– Pseudomonas aeruginosa
**** [[1iqz]], [[1ir0]] - BtFd – Bacillus thermoproteolyticus
**** [[1rgv]] - Fd – Thauera aromatica
**** [[1dax]], [[1dfd]] – DaFd – Desulfovibrio africanus – NMR
**** [[1fxr]] - DaFd
**** [[1vjw]] – Fd – Thermotoga maritima

*** 3Fe-4S containing ferredoxins

**** [[2v2k]] – Fd – Mycobacterium smegmatis
**** [[1wtf]] - BtFd (mutant)
**** [[1sj1]] - PfFd
**** [[1fxd]] - DgFd – Desulfovibrio gigas
**** [[1f2g]] – DgFd – NMR
**** [[1xer]] - Fd – Sulfolobus tokodaii

*** 4Fe-4S+3Fe-4S containing ferredoxins

**** [[1gao]], [[6fdr]], [[7fd1]], [[7fdr]], [[1axq]], [[6fd1]], [[1frh]], **** [[1fri]],[[1frj]], [[1frk]], [[1frl]], [[1frm]], [[1fda]], [[1fdb]], **** [[1fdd]], [[5fd1]], [[1fer]] – AvFd – Azotobacter vinelandii
**** [[1pc4]], [[1pc5]], [[1g6b]], [[1g3o]], [[1ff2]], [[1b0v]], [[1d3w]], **** [[1b0t]], [[1a6l]], [[1ftc]], [[1frx]], [[2fd2]], [[1fd2]] - AvFd (mutant)
**** [[1h98]] – Fd – Thermus thermophilus
**** [[1a8p]], [[1bd6]] - BsFd – Bacillus schlegelii – NMR

*** 4Fe-4S+4Fe-4S containing ferredoxins

**** [[1dur]] – Fd – Peptoniphilus asaccarolyticus
**** [[1bwe]], [[1bqx]] - BsFd (mutant) – NMR
**** [[2fdn]], [[1fca]] , [[1fdn]]- Fd – Clostridium acidi-urici
**** [[1blu]] - Fd – Chromatium vinosum
**** [[1clf ]]– Fd – Clostridium pasteurianum – NMR

*** Adrenoredoxin

**** [[2jqr]] – ADR Fd domain (mutant)+cytochrome c (mutant) – yeast – NMR
**** [[2bt6]] – cADR1 modified – cow
**** [[1l6u]], [[1l6v]] – cADR1 – NMR
**** [[1e6e]] – cADR (mutant)+ADR reductase
**** [[1cje]], [[1ayf]] - cADR

*** Putidaredoxin

**** [[1yji]], [[1yjj]], [[1pdx]] – PpPUT – Pseudomonas putida – NMR
**** [[3lb8]] – PpPUT (mutant)+PUT reductase
**** [[1xln]], [[1xlo]], [[1xlp]], [[1xlq]], [[1r7s]], [[1oqq]], [[1oqr]] - PpPUT (mutant)
**** [[1gpx]], [[1put]]- PpPUT (mutant) - NMR

*** Terpredoxin

**** [[1b9r]] – TER – Pseudomonas - NMR

* Toxins
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]
** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

* Diseases
** Cancer
*** [[SRC]]
*** [[Proteins involved in cancer]]

* Evolution
** [[Conservation, Evolutionary]]
** [[Extremophiles]]

* Gene Expression and Replication
** Nucleic Acid Structure
*** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]
*** [[Nucleosomes]]

** DNA Replication, Repair, and Recombination
*** [[DNA Replication,Transcription and Translation]]
*** [[DNA Polymerase I]]
*** [[PcrA helicase]]
*** [[Fpg Nei Protein Superfamily]] - DNA Repair and Base Excision DNA Repair
*** [[Human RecQ-Like protein 1]] - RecQ family of DNA helicases are conserved in from bacteria to man
*** [[Structure of E. coli DnaC helicase loader]]
*** [[1x9n#Crystal Structure of Human DNA Ligase I bound to 5.27-adenylated.2C nicked DNA]]
*** [[Rop protein]]

** Transcription and RNA Processing
*** T-box family
**** [[T-box proteins]]
**** [[Brachyury]]
**** [[TBX15]]
*** [[C-Myc]]
*** [[Lac repressor]]
*** [[Reverse transcriptase]]
*** [[TATA-Binding Protein]]
*** [[RSP1275]]
*** [[Transcription Termination Factor Rho]]

** Protein Synthesis
*** [[Ribosome]]
*** [[Large Ribosomal Subunit of Haloarcula|Large Ribosomal Subunit]]
*** [[SelB Recognition]]
** Regulation of Gene Expression
*** [[Lac repressor]]
*** [[Irr]] (Iron Response Regulator )
*** Oncogenes
**** [[P53]]
**** [[SRC]]
*** [[Tangible Models of Cdc42 Interacting With Intersectin]]

* Immune System
** Antibodies
*** [[IgA]]
*** [[Epitopes]]
** [[Major Histocompatibility Complex Class I]]
*** [[Human beta two microglobulin]]

* Metabolism
** Introduction to Metabolism

** Glucose Catabolism
*** [[Triose Phosphate Isomerase]]
***[[Phosphofructokinase %28PFK%29]]

** Glycogen Metabolism and Gluconeogenesis
*** [[Phosphoglucose isomerase]]
*** [[Calmodulin in motion]]
*** [[Biotin Protein Ligase]]

** Citric Acid Cycle
*** [[Aconitase]]

** Electron Transport and Oxidative Phosphorylation
*** [[NADH quinone oxidoreductase ]]

** Photosynthesis
*** [[Photosystem II]]
*** [[Ribulose-1,5-bisphosphate carboxylase/oxygenase]]
*** [[PrrA in Rhodobacter sphaeroides]]
*** [[Pyruvate phosphate dikinase]]

** Lipid Metabolism
*** [[Acid-beta-glucosidase]]
** Amino Acid Metabolism
*** [[Aromatic amino acid hydroxylases]]
*** [[Phenylalanine hydroxylase]]
*** [[Tyrosine hydroxylase]]
*** [[ATP Phosphoribosyl Transferase]]
*** [[Isochorismate pyruvate lyase]]
** Mammalian Fuel Metabolism: Integration and Regulation
** Nucleotide Metabolism
*** [[Dihydrofolate reductase]]

* Methods of Structure Determination
** X-ray
*** [[X-ray crystallography]]
**** [[Asymmetric Unit]]
**** [[Biological Unit]]
**** [[Electron density maps]]
*** SAXS
** NMR
*** [[NMR Ensembles of Models]]
** Electron Microscopy

* Methods of Structure & Sequence Analysis
** Structural Analysis & Visualization
*** [[CPK]] - Corey-Pauling-Koltun spacefilling molecular models and color scheme for elements
*** [[Chime]]
*** Jmol
**** [[S347/Visualising protein structure|Visualising Protein Structure]] - Introduction to Jmol
**** [[FirstGlance in Jmol]]
*** [[User:Wayne Decatur/Teaching Proteopedia|Teaching Proteopedia]]
*** [[User:Wayne Decatur/Generate Unfolded Structures|Generate Unfolded Structures]]
*** Homology Model
**** [[User:Wayne Decatur/Homology Modeling|Homology Modeling]]
**** [[User:Emi Nakayama/TRIM5a Homology Models|TRIM5a Homology Models]] - Differences in models as a function of their templates
*** [[DRuMS]] - set of standard color schemes for macromolecular visualization

** Sequence Analysis
*** [[User:Wayne Decatur/Sequence analysis tools|Sequence Analysis Tools]]

* Model Structures
** See [[Theoretical models]]
** [[African Malaria Mosquito Acetylcholinesterase]]
** [[Structure of E. coli DnaC helicase loader]]
** [[User:Yuan-Ping Pang/HAB•BoNTAe]]

* Miscellaneous
** [[Molecular Playground]]
** [[Research Groups]]
}}
</big>

T

2010-07-06T18:36:52Z

Helen Ginn: Changing to a redirect to the crystal structure

#REDIRECT [[1xbr]]

T

2010-07-06T18:28:55Z

Helen Ginn: /* Crystallographic structure */

=Introduction=

Two well-known orthologues of the T protein are present in mice (Brachyury) and Xenopus laevis (Xbra). The homologue of T in mice, Brachyury, was the first T-box crystal structure to be determined.

=Crystal structure=

The T-box region of the Brachyury protein was crystallised with a 24 bp palindromic DNA duplex as determined by in vitro PCR-based binding selection. It crystallised as a dimer; in one monomer residues 39-221 were visible out of a total of 226 residues, and in the other residues 39-222 were visible. Both monomers were bound to the DNA (unlike in the structure of [[TBX5]]) and interacted through a poorly conserved region of 250 Å2. The N-terminus of 38 residues and C-terminus of 4 residues were disordered in the crystal structure. Nevertheless, the crystallographic structure agrees with DNA footprinting experiments in terms of which bases are protected by the protein.

The core of the monomer is a seven-stranded β-barrel structure reminiscent of the immunoglobulin fold. Hence the T protein belongs to the superfamily of Ig-domain transcription factors. Strand D of the seven-stranded β-barrel is replaced by helix H2, and the strand-connecting regions also contain α-helices. The C-terminal amino acids are α-helical in structure, unlike TBX3 and TBX5 where they form a 310 helix. The dimer interface is mainly formed by the ends of strand C' of both proteins.

==Dimer interface==

Residues Pro125, Asp126 and Pro128 from both monomers are bridged by water molecules and the nitrogen of Asn129 forms a hydrogen-bond to Ser127 of the other subunit. To stabilise the structure a hydrophobic patch formed by Pro128, Phe130 and assisted by Met85 and Val173 exists between the two monomers. Some types of T-box proteins have exchanged amino acids for Met85 (Lys, Arg, His), Val173 (Ala) and Phe130 (Thr) which may not undergo dimer formation.

The Brachyury protein is a monomer in solution and thus only dimerises when in contact with DNA. This is supported by the fact that the contact area is only 250 Å2. Antibodies stabilise the dimer on the DNA, however the molecular mechanism of this is unknown: it is possible that the antibodies stabilise the dimer contacts when present on the DNA.

==Structural aspects of DNA binding==

The loops between the β strands make the important contacts with the DNA. 11 amino acids make polar contacts with the DNA, mainly in the minor groove. Helix H3 and H4 recognise the DNA in the minor groove, where H3 bridges the DNA backbone and is positioned by Tyr196/Asn209 contacts with the phosphates on the edges and hydrophobic contacts between guanine ribose and Ile206 in the middle. H4 points into the minor groove with hydrphobic contacts to base edges/backbone sugars and hydrogen bonds between the Phe211 carbonyl group and N2 of guanine. Note that it can be any amino acid which fills this position (i.e., not conserved), however only guanine is recognised.

It is important to note that H3/H4 is not a helix-turn-helix motif. The angle between the helices is 90° (HTH motifs: 120°) and there are 2 amino acids in the loop (HTH motifs: 4), and it interacts in the minor groove (HTH motifs interact in the major groove). The T-domain is very similar to the NF-κB p50, and superimposing these shows the major groove recognition carried out by arginines in both cases. Arginine recognition of the major groove is also present in other T-box proteins such as TBX5.

==Structure of the DNA in the Brachyury-DNA complex==

The DNA adopted a B-like conformation with a rise of 3.3 Å, and 10.5 residues per turn (very similar to usual B-form values). The minor groove is enlarged but the DNA remains unbent: the phosphate-phosphate distances are usually 5.7 Å in the B-DNA conformation, but in this case it expands to 10 Å. However, there is no bend unlike in the binding of other transcription factors such as the TATA box binding protein.

=Functions and pathways of T protein=

The best characterised targets of the Xbra or T protein are the Xenopus embryonic fibroblast growth factor (eFGF, of which the mammalian homologue is FGF-4) and the Brachyury-induced homeobox-containing genes (Bix1, Bix2, Bix3 and Bix4).

=Known malfunctional mutations=

The Xenopus laevis homologue of the T protein, Xbra, has a known mutation of Lys149 which destroys DNA-binding activity. This is equivalent to Asn155 and Asn353 of Eomes and VegT respectively.

Proteopedia:Table of Contents

2010-07-06T18:27:30Z

Helen Ginn: Adding TBX15... sorry about all the edits

This guide to the contents of Proteopedia is maintained manually (not automatically generated) and so is inevitably incomplete. Please be sure to use the [[Help:Searching|search slots at the left]] if you don't find what you are looking for below.

<big>
{{#tree:id=siteTree|openlevels=1|close=top|open=top|

* Introduction to Structural Biology
** See [[About Macromolecular Structure]]
** Water

*** [[Water in macromolecular models|Water in Macromolecular Models]]
** Key Chemical Concepts for Structural Biology

*** [[Amino Acids]]
*** [[Cation-pi interactions]]
*** [[Hydrogen bond]]
*** [[Hydrogen in macromolecular models|Hydrogen in Macromolecular Models]]
*** [[Isoelectric point]]
*** [[Salt bridges]]

* Biomolecules
** [[About Macromolecular Structure]]

** Nucleotides, Nucleic Acids and Genetic Information
*** DNA
**** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]

** Amino Acids
*** [[Amino Acids]]
*** [[Selenocysteine]]
** Proteins, Primary Structure
*** [[Conservation, Evolutionary]]
*** [[Isoelectric point]]

** Proteins, Three-Dimensional Structure
*** [[User:Tommie_Hata/Protein_Structure_Tutorial]]
*** [[S347/The four tiers of protein structure]]
*** [[Secondary structure]]
*** Protein structural motifs
**** [[User:James D Watson/Structural Templates]]

*** Protein Misfolding
**** [[Prion protein]]
**** [[A Physical Model of the Structure of GNNQQNY from Yeast Prion Sup35]]

** Colored Proteins & those that Change Color
*** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
*** [[Dronpa]]
*** [[Factor IX]]

** DNA Binding Proteins
*** [[Helix-turn-helix motif]]
*** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

** Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies
*** Antibodies
**** [[IgA]]
**** [[Epitopes]]
**** [[Major Histocompatibility Complex Class I]]
*** [[Calmodulin in motion]]
*** [[Myoglobin]]
*** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]
*** [[Kinesin-5]]
** Lipids and Biological Membranes
** Lipid Binding Proteins
*** [[CRABP I ( Cellular Retinoic Acid Binding Protein )]]
** Membrane Transport Proteins
*** [[A Physical Model of the β2-Adrenergic Receptor]]
*** [[Lactose Permease]]
*** [[Proton Channels]]
*** [[Ion channels]]
**** [[M2 Proton Channel]]
**** [[Voltage-gated calcium channels]]
*** [[Mechanosensitive channels: opening and closing]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]

** Prions and Intrinsically Disordered Proteins
*** [[Prion protein]]
*** [[Doppel]]
*** [[Intrinsically Disordered Protein]]

** Toxins
*** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

** Mitosis, Meiosis and Cargo Transport Proteins
*** [[Kinesin-5]]

** Viruses
*** [[User:Wayne Decatur/Suppression of RNA Silencing by Viruses]]
*** Filamentous bacteriophage
**** [[G3p]] - minor coat protein found on the surface of filamentous bacteriophage
*** HIV
**** [[HIV-1 protease]]
**** [[HIV-1 Gag]]
**** [[HIV-1 Gag Recruitment of Tsg101 and the Viral Budding Process]]
**** [[User:Eric Martz/Molecular Playground/HIVDrug]]
*** Herpes Simplex Virus
**** [[Herpes Simplex Virus Thymidine Kinase]]
*** Influenza
**** [[Influenza hemagglutinin]]
**** [[Avian Influenza Neuraminidase, Tamiflu and Relenza]]

* Colored Proteins & those that Change Color
** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
** [[Dronpa]]
** [[Factor IX]]

* DNA Binding Proteins
** [[Helix-turn-helix motif]]
** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

* Enzymes
** Enzymatic Catalysis
*** Acid-beta-glucosidase
**** reHuman Acid-beta-glucosidase made in CHO cells [[1ogs]]
**** reHuman Acid-beta-glucosidase made in CHO cells bound to conduritol B epoxide [[1y7v]]
**** reHuman Acid-beta-glucosidase made in carrot cells complexed with N-butyl-deoxynojirimycin [[2v3d]]
**** Velaglucerase Alfa [[2wkl]]
*** Acid Proteases
**** [[HIV-1 protease]]

**** [[Streptomyces griseus Aminopeptidase (SGAP)]]; [[Aminopeptidase]]
*** [[Aconitase]]
*** Cysteine Proteases
*** [[Hen Egg-White (HEW) Lysozyme]]
*** [[Choline Oxidase]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Metalloproteases]]
**** [[Matrix metalloproteinases]]
*** Oxidoreductases
**** [[NADH quinone oxidoreductase ]]
*** [[Phosphofructokinase %28PFK%29]]
*** [[Pyruvate phosphate dikinase]]
*** [[Serotonin N-acetyltransferase]]
*** Serine Hydrolases
**** [[Acetylcholinesterase]] (AChE)
***** [[Acetylcholine]]
***** [[Flexibility of aromatic residues in acetylcholinesterase]]
***** [[AChE inhibitors and substrates]]
****** [[1eve]] AChE-Aricept complex; [[1eve (Arabic)]]; [[1eve (Chinese)]]; [[1eve (Italian)]]; [[1eve (Russian)]]; [[1eve (Spanish)]]; [[1eve (Turkish)]]
****** [[AChE bivalent inhibitors]]
**** [[Tobacco Etch Virus (TEV) Protease]]
*** [[Serine Protease]]
**** [[Trypsin]]
*** [[Triose Phosphate Isomerase]]
** Enzyme Inhibitors
*** [[Alpha-1-antitrypsin]]
** Enzyme Kinetics, Inhibition, and Control
***[[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
** Biochemical Signaling
*** [[Nitric oxide synthase]], [[NOS structures]]
*** [[Recoverin, a calcium-activated myristoyl switch]]
*** [[Bcl-2]]
*** [[C-Myc]]
*** [[C-di-GMP signaling]]

** Enzymes - Molecular Machines
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Pyruvate phosphate dikinase]]

* Fibrous Proteins
** [[Coiled coil]]
** [[Collagen]]

* Membrane Transport Proteins
** [[A Physical Model of the β2-Adrenergic Receptor]]
** [[Lactose Permease]]
** [[Proton Channels]]
** [[Ion channels]]
*** [[M2 Proton Channel]]
*** [[Voltage-gated calcium channels]]
** [[Mechanosensitive channels: opening and closing]]
** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]

* Myoglobin & Hemoglobin
** [[Myoglobin]]
** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]

* Nervous System Proteins

** [[Acetylcholinesterase]] (AChE)
*** [[Acetylcholine]]
*** [[Flexibility of aromatic residues in acetylcholinesterase]]

*** AChE inhibitors (In Different Languages)
**** [[1eve]] AChE-Aricept complex, [[1eve (Arabic)]], [[1eve (Chinese)]], [[1eve (Italian)]], [[1eve (Russian)]], [[1eve (Spanish)]], [[1eve (Turkish)]]
**** [[1vot]] AChE-Huperzine A complex, [[1vot (Chinese)]]

*** Acetylcholinesterase - AChE native
**** [[3lii]] – hAChE - recombinant human
**** [[1ea5]], [[2ace]] – ''Tc''AChE – trigonal – ''Torpedo californica''
**** [[2j3d]] – ''Tc''AChE – monoclinic
**** [[1w75]] – ''Tc''AChE – orthorhombic
**** [[1eea]] – ''Tc''AChE – cubic
**** [[2vt6]], [[2vt7]] – ''Tc''AChE – different dosage
**** [[1qid]] to [[1qim]] - ''Tc''AChE synchrotron radiation damage
**** [[1j06]], [[1maa]] – mAChE - mouse
**** [[1qo9]] – ''Dm''AChE - ''Drosophila''
**** [[1c2o]], [[1c2b]] – electrophorus AChE – Electric eel

*** AChE active site inhibitors conjugating at the bottom of the active site gorge
**** [[2w9i]] – ''Tc''AChE + methylene blue
**** [[2wls]] – MosAChE + AMTS13
**** [[2vq6]] – ''Tc''AChE + 2-PAM
**** [[2j3q]] – ''Tc''AChE + Thioflavin T
**** [[2ha0]] – mAChE + ketoamyltrimethylammonium
**** [[2h9y]] – mAChE + TMTFA
**** [[1gpk]], [[1gpn]], [[1vot]] – ''Tc''AChE + huperzine
**** [[1gqr]] – ''Tc''AChE + rivastigmine
**** [[1gqs]] – ''Tc''AChE + NAP
**** [[1e66]] – ''Tc''AChE + huprine
**** [[1dx4]], [[1qon]] – ''Dm''AChE + tacrine derivative
**** [[1oce]] – ''Tc''AChE + MF268
**** [[1ax9]], [[1ack]] – ''Tc''AChE + edrophonium
**** [[1amn]] – ''Tc''AChE + TMTFA
**** [[1acj]] – ''Tc''AChE + tacrine

*** AChE peripheral site inhibitors conjugating at the surface of the protein
**** [[1ku6]] - mAChE + fasciculin 2
**** [[1ku6]], [[1mah]] - mAChE + fasciculin 2
**** [[1j07]] - mAChE + decidium
**** [[1n5m]] - mAChE + gallamine
**** [[1n5r]] - mAChE + propidium
**** [[1b41]], [[1f8u]] - hAChE + fasciculin 2
**** [[1fss]] - TcAChE + fasciculin 2

*** AChE bis inhibitors spanning the active site gorge
**** [[AChE bivalent inhibitors]]
**** [[3i6m]] – ''Tc''AChE + N-piperidinopropyl galanthamine
**** [[3i6z]] - ''Tc''AChE + saccharinohexyl galanthamine
**** [[1zgb]], [[1zgc]] – ''Tc''AChE + tacrine (10) hupyridone
**** [[2w6c]] – ''Tc''AChE + bis-(-)-nor-meptazinol
**** [[2ckm]], [[2cmf]] – ''Tc''AChE + bis-tacrine
**** [[2cek]] – ''Tc''AChE + N-[8-(1,2,3,4-tetrahydroacridin-9-ylthio)octyl]-1,2,3,4-tetrahydroacridin-9-amine
**** [[1ut6]] - ''Tc''AChE + N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1odc]] - ''Tc''AChE + N-4-quinolyl-N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1w4l]], [[1w6r]], [[1w76]], [[1dx6]], [[1qti]] - TcAChE + galanthamine and derivative
**** [[1q83]], [[1q84]] - mAChE + TZ2PA6
**** [[1h22]], [[1h23]] – ''Tc''AChE + bis-hupyridone
**** [[1hbj]] – ''Tc''AChE + quinoline derivativev
**** [[1e3q]] – ''Tc''AChE + bw284c51
**** [[1eve]] – ''Tc''AChE + e2020
**** [[1acl]] – ''Tc''AChE + decamethonium

*** AChE organophosphate inhibitors causing irreversible inhibition
**** [[2wu3]] – mAChE + fenamiphos and HI-6
**** [[2wu4]] – mAChE + fenamiphos and ortho-7
**** [[2jgf]] - mAChE + fenamiphos
**** [[2wfz]], [[2wg0]], [[1som]] - ''Tc''AChE + soman
**** [[2wg1]] - ''Tc''AChE + soman + 2-PAM
**** [[2whp]], [[2whq]], [[2whr]] – mAChE + sarin and HI-6
**** [[2jgg]] - mAChE + sarin
**** [[2jgl]] - mAChE + VX and sarin
**** [[1cfj]] - ''Tc''AChE + sarin, GB
**** [[3dl4]], [[3dl7]] – mAChE + tabun
**** [[2jey]] – mAChE + HLO-7
**** [[2c0p]], [[2c0q]] - mAChE + tabun
**** [[2jez]] - mAChE + tabun + HLO-7
**** [[2jf0]] - mAChE + tabun + Ortho-7
**** [[2jgh]] - mAChE + VX
**** [[1vxo]], [[1vxr]] - ''Tc''AChE + VX
**** [[2jgi]], [[2jgm]] - mAChE + DFP
**** [[1dfp]] - ''Tc''AChE + DFP
**** [[2jgj]], [[2jgk]], [[2jge]] - mAChE + methamidophos
**** [[2gyu]] - mAChE + HI-6
**** [[2gyv]] - mAChE + Ortho-7
**** [[2gyw]] - mAChE + obidoxime

*** AChE substrate analogues mimicking the binding of the substrate acetylcholine
**** [[2ha4]] – mAChE (mutant) + acetylcholine
**** [[2vja]], [[2vjb]], [[2vjc]], [[2vjd]], [[2cf5]] – ''Tc''AChE + 4-oxo-N,N,N-trimethylpentanaminium
**** [[2v96]], [[2v97]], [[2v98]], [[2v99]] – ''Tc''AChE + 1-(2-nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine
**** [[2ha2]] – mAChE + succinylcholine
**** [[2ha3]] - mAChE + choline
**** [[2ha5]] – mAChE (mutant) + acetylthiocholine
**** [[2ha6]] – mAChE (mutant) + succinylthiocholine
**** [[2ha7]] – mAChE (mutant) + butyrylthiocholine
**** [[2ch4]], [[2c58]] – ''Tc''AChE + acetylthiocholine
**** [[2c5g]] – ''Tc''AChE + thiocholine

*** Others…
**** [[2j4f]] – ''Tc''AChE + Hg
**** [[1vzj]] – ''Tc''AChE tetramerization domain
**** [[1jjb]] – ''Tc''AChE + PEG

** [[Acetylcholine binding protein]] (AChBP)
** [[Butyrylcholinesterase]] (BChE)

* Prions and Intrinsically Disordered Proteins
** [[Prion protein]]
** [[Doppel]]
** [[Intrinsically Disordered Protein]]

* Small Iron Sulfur Proteins
** [[Ferredoxin]] (Fd)
*** 2Fe-2S containing ferredoxins
**** [[3hui]] – Fd – ''Rhodopseudomonas palustris''
**** [[2kaj]], [[1dox]], [[1doy]] – SyFd +Ga – Synechocystis – NMR
**** [[1off]] – SyFd
**** [[3gce]] – Fd – Nocardioides aromaticivorans
**** [[2e4p]], [[2e4q]] - Fd – ''Pseudomonas sp.''
**** [[2q3w]], [[1vm9]] - PmFd (mutant) – ''Pseudomonas mendocina''
**** [[2i7f]] - Fd – ''Rhodobacter capsulatus''
**** [[1rfk]] - Fd – Cyanobacterium ''masticogladus laminosus''
**** [[1vck]] - Fd – ''Pseudomonas resinovorans''
**** [[1wri]], [[1frr]] - Fd – Equisetum arvense
**** [[1sjg]] - PmFd– NMR
**** [[1iue]] - Fd– Plasmodium falciparum
**** [[1m2a]] –AeFd – Aquifex aeolicus
**** [[1m2b]], [[1m2d]], [[1f37]], [[1f5b]], [[1f5c]] – AeFd (mutant)
**** [[1l5p]] – Fd – Trichomonas vaginalis
**** [[1i7h]] - Fd – Escherichia coli
**** [[1czp]], [[1qt9]], [[1frd]], [[1fxa]] - aFd– anabaena
**** [[1j7a]], [[1j7b]], [[1j7c]] , [[1qoa]], [[1qob]], [[1qof]], [[1qog]]- aFd (mutant)
**** [[1e0z]] – Fd – Halobacterium salinarium
**** [[1pfd]] – Fd – Petroselinum crispum – NMR
**** [[1a70]] - Fd (mutant) – Spinacia oleracea
**** [[1awd]] - Fd – Chlorella fusca
**** [[2cjn]], [[2cjo]], [[1roe]] – SyFd – NMR
**** [[1rof]] – SyFd – Synechococcus elongates
**** [[1doi]] - Fd – Haloarcula marismortui
**** [[4fxc]] – Fd – Spirulina platensis
**** [[1fxi]] – Fd – Aphanothece sacrum
**** [[3dqy]], [[2qpz]] - Fd – Pseudomonas putida

*** 4Fe-4S containing ferredoxins

**** [[3eun]] – AvFd – Allochromatium vinosum
**** [[3exy]] - AvFd (mutant)
**** [[2vkr]] - Fd+Zn – Acidianus ambivalens
**** [[2z8q]] - PfFd (mutant) – Pyrococcus furiosus
**** [[2fgo]] - Fd– Pseudomonas aeruginosa
**** [[1iqz]], [[1ir0]] - BtFd – Bacillus thermoproteolyticus
**** [[1rgv]] - Fd – Thauera aromatica
**** [[1dax]], [[1dfd]] – DaFd – Desulfovibrio africanus – NMR
**** [[1fxr]] - DaFd
**** [[1vjw]] – Fd – Thermotoga maritima

*** 3Fe-4S containing ferredoxins

**** [[2v2k]] – Fd – Mycobacterium smegmatis
**** [[1wtf]] - BtFd (mutant)
**** [[1sj1]] - PfFd
**** [[1fxd]] - DgFd – Desulfovibrio gigas
**** [[1f2g]] – DgFd – NMR
**** [[1xer]] - Fd – Sulfolobus tokodaii

*** 4Fe-4S+3Fe-4S containing ferredoxins

**** [[1gao]], [[6fdr]], [[7fd1]], [[7fdr]], [[1axq]], [[6fd1]], [[1frh]], **** [[1fri]],[[1frj]], [[1frk]], [[1frl]], [[1frm]], [[1fda]], [[1fdb]], **** [[1fdd]], [[5fd1]], [[1fer]] – AvFd – Azotobacter vinelandii
**** [[1pc4]], [[1pc5]], [[1g6b]], [[1g3o]], [[1ff2]], [[1b0v]], [[1d3w]], **** [[1b0t]], [[1a6l]], [[1ftc]], [[1frx]], [[2fd2]], [[1fd2]] - AvFd (mutant)
**** [[1h98]] – Fd – Thermus thermophilus
**** [[1a8p]], [[1bd6]] - BsFd – Bacillus schlegelii – NMR

*** 4Fe-4S+4Fe-4S containing ferredoxins

**** [[1dur]] – Fd – Peptoniphilus asaccarolyticus
**** [[1bwe]], [[1bqx]] - BsFd (mutant) – NMR
**** [[2fdn]], [[1fca]] , [[1fdn]]- Fd – Clostridium acidi-urici
**** [[1blu]] - Fd – Chromatium vinosum
**** [[1clf ]]– Fd – Clostridium pasteurianum – NMR

*** Adrenoredoxin

**** [[2jqr]] – ADR Fd domain (mutant)+cytochrome c (mutant) – yeast – NMR
**** [[2bt6]] – cADR1 modified – cow
**** [[1l6u]], [[1l6v]] – cADR1 – NMR
**** [[1e6e]] – cADR (mutant)+ADR reductase
**** [[1cje]], [[1ayf]] - cADR

*** Putidaredoxin

**** [[1yji]], [[1yjj]], [[1pdx]] – PpPUT – Pseudomonas putida – NMR
**** [[3lb8]] – PpPUT (mutant)+PUT reductase
**** [[1xln]], [[1xlo]], [[1xlp]], [[1xlq]], [[1r7s]], [[1oqq]], [[1oqr]] - PpPUT (mutant)
**** [[1gpx]], [[1put]]- PpPUT (mutant) - NMR

*** Terpredoxin

**** [[1b9r]] – TER – Pseudomonas - NMR

* Toxins
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]
** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

* Diseases
** Cancer
*** [[SRC]]
*** [[Proteins involved in cancer]]

* Evolution
** [[Conservation, Evolutionary]]
** [[Extremophiles]]

* Gene Expression and Replication
** Nucleic Acid Structure
*** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]
*** [[Nucleosomes]]

** DNA Replication, Repair, and Recombination
*** [[DNA Replication,Transcription and Translation]]
*** [[DNA Polymerase I]]
*** [[PcrA helicase]]
*** [[Fpg Nei Protein Superfamily]] - DNA Repair and Base Excision DNA Repair
*** [[Human RecQ-Like protein 1]] - RecQ family of DNA helicases are conserved in from bacteria to man
*** [[Structure of E. coli DnaC helicase loader]]
*** [[1x9n#Crystal Structure of Human DNA Ligase I bound to 5.27-adenylated.2C nicked DNA]]
*** [[Rop protein]]

** Transcription and RNA Processing
*** T-box family
**** [[T-box proteins]]
**** [[T]]
**** [[TBX15]]
*** [[C-Myc]]
*** [[Lac repressor]]
*** [[Reverse transcriptase]]
*** [[TATA-Binding Protein]]
*** [[RSP1275]]
*** [[Transcription Termination Factor Rho]]

** Protein Synthesis
*** [[Ribosome]]
*** [[Large Ribosomal Subunit of Haloarcula|Large Ribosomal Subunit]]
*** [[SelB Recognition]]
** Regulation of Gene Expression
*** [[Lac repressor]]
*** [[Irr]] (Iron Response Regulator )
*** Oncogenes
**** [[P53]]
**** [[SRC]]
*** [[Tangible Models of Cdc42 Interacting With Intersectin]]

* Immune System
** Antibodies
*** [[IgA]]
*** [[Epitopes]]
** [[Major Histocompatibility Complex Class I]]
*** [[Human beta two microglobulin]]

* Metabolism
** Introduction to Metabolism

** Glucose Catabolism
*** [[Triose Phosphate Isomerase]]
***[[Phosphofructokinase %28PFK%29]]

** Glycogen Metabolism and Gluconeogenesis
*** [[Phosphoglucose isomerase]]
*** [[Calmodulin in motion]]
*** [[Biotin Protein Ligase]]

** Citric Acid Cycle
*** [[Aconitase]]

** Electron Transport and Oxidative Phosphorylation
*** [[NADH quinone oxidoreductase ]]

** Photosynthesis
*** [[Photosystem II]]
*** [[Ribulose-1,5-bisphosphate carboxylase/oxygenase]]
*** [[PrrA in Rhodobacter sphaeroides]]
*** [[Pyruvate phosphate dikinase]]

** Lipid Metabolism
*** [[Acid-beta-glucosidase]]
** Amino Acid Metabolism
*** [[Aromatic amino acid hydroxylases]]
*** [[Phenylalanine hydroxylase]]
*** [[Tyrosine hydroxylase]]
*** [[ATP Phosphoribosyl Transferase]]
*** [[Isochorismate pyruvate lyase]]
** Mammalian Fuel Metabolism: Integration and Regulation
** Nucleotide Metabolism
*** [[Dihydrofolate reductase]]

* Methods of Structure Determination
** X-ray
*** [[X-ray crystallography]]
**** [[Asymmetric Unit]]
**** [[Biological Unit]]
**** [[Electron density maps]]
*** SAXS
** NMR
*** [[NMR Ensembles of Models]]
** Electron Microscopy

* Methods of Structure & Sequence Analysis
** Structural Analysis & Visualization
*** [[CPK]] - Corey-Pauling-Koltun spacefilling molecular models and color scheme for elements
*** [[Chime]]
*** Jmol
**** [[S347/Visualising protein structure|Visualising Protein Structure]] - Introduction to Jmol
**** [[FirstGlance in Jmol]]
*** [[User:Wayne Decatur/Teaching Proteopedia|Teaching Proteopedia]]
*** [[User:Wayne Decatur/Generate Unfolded Structures|Generate Unfolded Structures]]
*** Homology Model
**** [[User:Wayne Decatur/Homology Modeling|Homology Modeling]]
**** [[User:Emi Nakayama/TRIM5a Homology Models|TRIM5a Homology Models]] - Differences in models as a function of their templates
*** [[DRuMS]] - set of standard color schemes for macromolecular visualization

** Sequence Analysis
*** [[User:Wayne Decatur/Sequence analysis tools|Sequence Analysis Tools]]

* Model Structures
** See [[Theoretical models]]
** [[African Malaria Mosquito Acetylcholinesterase]]
** [[Structure of E. coli DnaC helicase loader]]
** [[User:Yuan-Ping Pang/HAB•BoNTAe]]

* Miscellaneous
** [[Molecular Playground]]
** [[Research Groups]]
}}
</big>

T-box proteins

2010-07-06T18:26:49Z

Helen Ginn:

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of T-box proteins are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''.

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and Tbx3 and Tbx5 on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| [[TBX1]]
| Crystal structure solved
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| [[TBX15]]
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| [[TBX3]]
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| [[TBX5]]
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}

TBX15

2010-07-06T18:25:49Z

Helen Ginn: TBX15 page start-up

=Introduction=

TBX15 is implicated in Cousin syndrome. Cousin syndrome was first discovered in humans. Tbx15 deficiency in mice were isolated, and were seen to have similar symptoms. DNA of two girls with Cousin syndrome were searched directly for TBX15 deficiency or mutations and two related mutations were discovered. The mutant mRNA was present at a level same or higher than that of wild-type mRNA, and the expressed protein had a lower stability than the wild-type TBX15.

=Functions and pathways of TBX15=

Target genes of TBX15 are so far elusive but are believed to be possibly shared with those of SOX9, FGFR2 and POR.

=Known malfunctional mutations=

The two related mutations discovered by sequencing Cousin syndrome sufferers were

* Deletion at codon 344 resulting in a frame shift of the remaining 78 amino acids
* Deletion resulting in a frame shift of remaining 77 amino acids

On checking the stability and localisation of the TBX15 mutants, it was found that it was no longer targetted to the nucleus. Simple truncation of the C-terminal 152 amino acids does not affect stability alone; however, presence of the missense 78 amino acids target the protein to proteasomal degradation, suggesting the mutant is an inherently unstable protein. This was confirmed by fusing EGFP (enhanced green fluorescent protein) to the mutant TBX15 on its C-terminus, which was found to be undetectable in cells.

It is possible, but not confirmed, that dominant mutations in the T-box region of TBX15 may correspond to a Kosenow syndrome phenotype, a candidate disease.

Proteopedia:Table of Contents

2010-07-06T18:22:15Z

Helen Ginn: Adding T to the Transcription and RNA processing folder.

This guide to the contents of Proteopedia is maintained manually (not automatically generated) and so is inevitably incomplete. Please be sure to use the [[Help:Searching|search slots at the left]] if you don't find what you are looking for below.

<big>
{{#tree:id=siteTree|openlevels=1|close=top|open=top|

* Introduction to Structural Biology
** See [[About Macromolecular Structure]]
** Water

*** [[Water in macromolecular models|Water in Macromolecular Models]]
** Key Chemical Concepts for Structural Biology

*** [[Amino Acids]]
*** [[Cation-pi interactions]]
*** [[Hydrogen bond]]
*** [[Hydrogen in macromolecular models|Hydrogen in Macromolecular Models]]
*** [[Isoelectric point]]
*** [[Salt bridges]]

* Biomolecules
** [[About Macromolecular Structure]]

** Nucleotides, Nucleic Acids and Genetic Information
*** DNA
**** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]

** Amino Acids
*** [[Amino Acids]]
*** [[Selenocysteine]]
** Proteins, Primary Structure
*** [[Conservation, Evolutionary]]
*** [[Isoelectric point]]

** Proteins, Three-Dimensional Structure
*** [[User:Tommie_Hata/Protein_Structure_Tutorial]]
*** [[S347/The four tiers of protein structure]]
*** [[Secondary structure]]
*** Protein structural motifs
**** [[User:James D Watson/Structural Templates]]

*** Protein Misfolding
**** [[Prion protein]]
**** [[A Physical Model of the Structure of GNNQQNY from Yeast Prion Sup35]]

** Colored Proteins & those that Change Color
*** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
*** [[Dronpa]]
*** [[Factor IX]]

** DNA Binding Proteins
*** [[Helix-turn-helix motif]]
*** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

** Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies
*** Antibodies
**** [[IgA]]
**** [[Epitopes]]
**** [[Major Histocompatibility Complex Class I]]
*** [[Calmodulin in motion]]
*** [[Myoglobin]]
*** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]
*** [[Kinesin-5]]
** Lipids and Biological Membranes
** Lipid Binding Proteins
*** [[CRABP I ( Cellular Retinoic Acid Binding Protein )]]
** Membrane Transport Proteins
*** [[A Physical Model of the β2-Adrenergic Receptor]]
*** [[Lactose Permease]]
*** [[Proton Channels]]
*** [[Ion channels]]
**** [[M2 Proton Channel]]
**** [[Voltage-gated calcium channels]]
*** [[Mechanosensitive channels: opening and closing]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]

** Prions and Intrinsically Disordered Proteins
*** [[Prion protein]]
*** [[Doppel]]
*** [[Intrinsically Disordered Protein]]

** Toxins
*** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

** Mitosis, Meiosis and Cargo Transport Proteins
*** [[Kinesin-5]]

** Viruses
*** [[User:Wayne Decatur/Suppression of RNA Silencing by Viruses]]
*** Filamentous bacteriophage
**** [[G3p]] - minor coat protein found on the surface of filamentous bacteriophage
*** HIV
**** [[HIV-1 protease]]
**** [[HIV-1 Gag]]
**** [[HIV-1 Gag Recruitment of Tsg101 and the Viral Budding Process]]
**** [[User:Eric Martz/Molecular Playground/HIVDrug]]
*** Herpes Simplex Virus
**** [[Herpes Simplex Virus Thymidine Kinase]]
*** Influenza
**** [[Influenza hemagglutinin]]
**** [[Avian Influenza Neuraminidase, Tamiflu and Relenza]]

* Colored Proteins & those that Change Color
** [[Green Fluorescent Protein]]; [[GFP (Hebrew)]]
** [[Dronpa]]
** [[Factor IX]]

* DNA Binding Proteins
** [[Helix-turn-helix motif]]
** [[DNA-binding protein VirE2 from Agrobacterium tumefaciens complexed with chaperone VirE1]]

* Enzymes
** Enzymatic Catalysis
*** Acid-beta-glucosidase
**** reHuman Acid-beta-glucosidase made in CHO cells [[1ogs]]
**** reHuman Acid-beta-glucosidase made in CHO cells bound to conduritol B epoxide [[1y7v]]
**** reHuman Acid-beta-glucosidase made in carrot cells complexed with N-butyl-deoxynojirimycin [[2v3d]]
**** Velaglucerase Alfa [[2wkl]]
*** Acid Proteases
**** [[HIV-1 protease]]

**** [[Streptomyces griseus Aminopeptidase (SGAP)]]; [[Aminopeptidase]]
*** [[Aconitase]]
*** Cysteine Proteases
*** [[Hen Egg-White (HEW) Lysozyme]]
*** [[Choline Oxidase]]
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Metalloproteases]]
**** [[Matrix metalloproteinases]]
*** Oxidoreductases
**** [[NADH quinone oxidoreductase ]]
*** [[Phosphofructokinase %28PFK%29]]
*** [[Pyruvate phosphate dikinase]]
*** [[Serotonin N-acetyltransferase]]
*** Serine Hydrolases
**** [[Acetylcholinesterase]] (AChE)
***** [[Acetylcholine]]
***** [[Flexibility of aromatic residues in acetylcholinesterase]]
***** [[AChE inhibitors and substrates]]
****** [[1eve]] AChE-Aricept complex; [[1eve (Arabic)]]; [[1eve (Chinese)]]; [[1eve (Italian)]]; [[1eve (Russian)]]; [[1eve (Spanish)]]; [[1eve (Turkish)]]
****** [[AChE bivalent inhibitors]]
**** [[Tobacco Etch Virus (TEV) Protease]]
*** [[Serine Protease]]
**** [[Trypsin]]
*** [[Triose Phosphate Isomerase]]
** Enzyme Inhibitors
*** [[Alpha-1-antitrypsin]]
** Enzyme Kinetics, Inhibition, and Control
***[[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
** Biochemical Signaling
*** [[Nitric oxide synthase]], [[NOS structures]]
*** [[Recoverin, a calcium-activated myristoyl switch]]
*** [[Bcl-2]]
*** [[C-Myc]]
*** [[C-di-GMP signaling]]

** Enzymes - Molecular Machines
*** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
*** [[Pyruvate phosphate dikinase]]

* Fibrous Proteins
** [[Coiled coil]]
** [[Collagen]]

* Membrane Transport Proteins
** [[A Physical Model of the β2-Adrenergic Receptor]]
** [[Lactose Permease]]
** [[Proton Channels]]
** [[Ion channels]]
*** [[M2 Proton Channel]]
*** [[Voltage-gated calcium channels]]
** [[Mechanosensitive channels: opening and closing]]
** [[Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System]]
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]

* Myoglobin & Hemoglobin
** [[Myoglobin]]
** [[Hemoglobin]]; [[Hemoglobin (Hebrew)]]

* Nervous System Proteins

** [[Acetylcholinesterase]] (AChE)
*** [[Acetylcholine]]
*** [[Flexibility of aromatic residues in acetylcholinesterase]]

*** AChE inhibitors (In Different Languages)
**** [[1eve]] AChE-Aricept complex, [[1eve (Arabic)]], [[1eve (Chinese)]], [[1eve (Italian)]], [[1eve (Russian)]], [[1eve (Spanish)]], [[1eve (Turkish)]]
**** [[1vot]] AChE-Huperzine A complex, [[1vot (Chinese)]]

*** Acetylcholinesterase - AChE native
**** [[3lii]] – hAChE - recombinant human
**** [[1ea5]], [[2ace]] – ''Tc''AChE – trigonal – ''Torpedo californica''
**** [[2j3d]] – ''Tc''AChE – monoclinic
**** [[1w75]] – ''Tc''AChE – orthorhombic
**** [[1eea]] – ''Tc''AChE – cubic
**** [[2vt6]], [[2vt7]] – ''Tc''AChE – different dosage
**** [[1qid]] to [[1qim]] - ''Tc''AChE synchrotron radiation damage
**** [[1j06]], [[1maa]] – mAChE - mouse
**** [[1qo9]] – ''Dm''AChE - ''Drosophila''
**** [[1c2o]], [[1c2b]] – electrophorus AChE – Electric eel

*** AChE active site inhibitors conjugating at the bottom of the active site gorge
**** [[2w9i]] – ''Tc''AChE + methylene blue
**** [[2wls]] – MosAChE + AMTS13
**** [[2vq6]] – ''Tc''AChE + 2-PAM
**** [[2j3q]] – ''Tc''AChE + Thioflavin T
**** [[2ha0]] – mAChE + ketoamyltrimethylammonium
**** [[2h9y]] – mAChE + TMTFA
**** [[1gpk]], [[1gpn]], [[1vot]] – ''Tc''AChE + huperzine
**** [[1gqr]] – ''Tc''AChE + rivastigmine
**** [[1gqs]] – ''Tc''AChE + NAP
**** [[1e66]] – ''Tc''AChE + huprine
**** [[1dx4]], [[1qon]] – ''Dm''AChE + tacrine derivative
**** [[1oce]] – ''Tc''AChE + MF268
**** [[1ax9]], [[1ack]] – ''Tc''AChE + edrophonium
**** [[1amn]] – ''Tc''AChE + TMTFA
**** [[1acj]] – ''Tc''AChE + tacrine

*** AChE peripheral site inhibitors conjugating at the surface of the protein
**** [[1ku6]] - mAChE + fasciculin 2
**** [[1ku6]], [[1mah]] - mAChE + fasciculin 2
**** [[1j07]] - mAChE + decidium
**** [[1n5m]] - mAChE + gallamine
**** [[1n5r]] - mAChE + propidium
**** [[1b41]], [[1f8u]] - hAChE + fasciculin 2
**** [[1fss]] - TcAChE + fasciculin 2

*** AChE bis inhibitors spanning the active site gorge
**** [[AChE bivalent inhibitors]]
**** [[3i6m]] – ''Tc''AChE + N-piperidinopropyl galanthamine
**** [[3i6z]] - ''Tc''AChE + saccharinohexyl galanthamine
**** [[1zgb]], [[1zgc]] – ''Tc''AChE + tacrine (10) hupyridone
**** [[2w6c]] – ''Tc''AChE + bis-(-)-nor-meptazinol
**** [[2ckm]], [[2cmf]] – ''Tc''AChE + bis-tacrine
**** [[2cek]] – ''Tc''AChE + N-[8-(1,2,3,4-tetrahydroacridin-9-ylthio)octyl]-1,2,3,4-tetrahydroacridin-9-amine
**** [[1ut6]] - ''Tc''AChE + N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1odc]] - ''Tc''AChE + N-4-quinolyl-N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane
**** [[1w4l]], [[1w6r]], [[1w76]], [[1dx6]], [[1qti]] - TcAChE + galanthamine and derivative
**** [[1q83]], [[1q84]] - mAChE + TZ2PA6
**** [[1h22]], [[1h23]] – ''Tc''AChE + bis-hupyridone
**** [[1hbj]] – ''Tc''AChE + quinoline derivativev
**** [[1e3q]] – ''Tc''AChE + bw284c51
**** [[1eve]] – ''Tc''AChE + e2020
**** [[1acl]] – ''Tc''AChE + decamethonium

*** AChE organophosphate inhibitors causing irreversible inhibition
**** [[2wu3]] – mAChE + fenamiphos and HI-6
**** [[2wu4]] – mAChE + fenamiphos and ortho-7
**** [[2jgf]] - mAChE + fenamiphos
**** [[2wfz]], [[2wg0]], [[1som]] - ''Tc''AChE + soman
**** [[2wg1]] - ''Tc''AChE + soman + 2-PAM
**** [[2whp]], [[2whq]], [[2whr]] – mAChE + sarin and HI-6
**** [[2jgg]] - mAChE + sarin
**** [[2jgl]] - mAChE + VX and sarin
**** [[1cfj]] - ''Tc''AChE + sarin, GB
**** [[3dl4]], [[3dl7]] – mAChE + tabun
**** [[2jey]] – mAChE + HLO-7
**** [[2c0p]], [[2c0q]] - mAChE + tabun
**** [[2jez]] - mAChE + tabun + HLO-7
**** [[2jf0]] - mAChE + tabun + Ortho-7
**** [[2jgh]] - mAChE + VX
**** [[1vxo]], [[1vxr]] - ''Tc''AChE + VX
**** [[2jgi]], [[2jgm]] - mAChE + DFP
**** [[1dfp]] - ''Tc''AChE + DFP
**** [[2jgj]], [[2jgk]], [[2jge]] - mAChE + methamidophos
**** [[2gyu]] - mAChE + HI-6
**** [[2gyv]] - mAChE + Ortho-7
**** [[2gyw]] - mAChE + obidoxime

*** AChE substrate analogues mimicking the binding of the substrate acetylcholine
**** [[2ha4]] – mAChE (mutant) + acetylcholine
**** [[2vja]], [[2vjb]], [[2vjc]], [[2vjd]], [[2cf5]] – ''Tc''AChE + 4-oxo-N,N,N-trimethylpentanaminium
**** [[2v96]], [[2v97]], [[2v98]], [[2v99]] – ''Tc''AChE + 1-(2-nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine
**** [[2ha2]] – mAChE + succinylcholine
**** [[2ha3]] - mAChE + choline
**** [[2ha5]] – mAChE (mutant) + acetylthiocholine
**** [[2ha6]] – mAChE (mutant) + succinylthiocholine
**** [[2ha7]] – mAChE (mutant) + butyrylthiocholine
**** [[2ch4]], [[2c58]] – ''Tc''AChE + acetylthiocholine
**** [[2c5g]] – ''Tc''AChE + thiocholine

*** Others…
**** [[2j4f]] – ''Tc''AChE + Hg
**** [[1vzj]] – ''Tc''AChE tetramerization domain
**** [[1jjb]] – ''Tc''AChE + PEG

** [[Acetylcholine binding protein]] (AChBP)
** [[Butyrylcholinesterase]] (BChE)

* Prions and Intrinsically Disordered Proteins
** [[Prion protein]]
** [[Doppel]]
** [[Intrinsically Disordered Protein]]

* Small Iron Sulfur Proteins
** [[Ferredoxin]] (Fd)
*** 2Fe-2S containing ferredoxins
**** [[3hui]] – Fd – ''Rhodopseudomonas palustris''
**** [[2kaj]], [[1dox]], [[1doy]] – SyFd +Ga – Synechocystis – NMR
**** [[1off]] – SyFd
**** [[3gce]] – Fd – Nocardioides aromaticivorans
**** [[2e4p]], [[2e4q]] - Fd – ''Pseudomonas sp.''
**** [[2q3w]], [[1vm9]] - PmFd (mutant) – ''Pseudomonas mendocina''
**** [[2i7f]] - Fd – ''Rhodobacter capsulatus''
**** [[1rfk]] - Fd – Cyanobacterium ''masticogladus laminosus''
**** [[1vck]] - Fd – ''Pseudomonas resinovorans''
**** [[1wri]], [[1frr]] - Fd – Equisetum arvense
**** [[1sjg]] - PmFd– NMR
**** [[1iue]] - Fd– Plasmodium falciparum
**** [[1m2a]] –AeFd – Aquifex aeolicus
**** [[1m2b]], [[1m2d]], [[1f37]], [[1f5b]], [[1f5c]] – AeFd (mutant)
**** [[1l5p]] – Fd – Trichomonas vaginalis
**** [[1i7h]] - Fd – Escherichia coli
**** [[1czp]], [[1qt9]], [[1frd]], [[1fxa]] - aFd– anabaena
**** [[1j7a]], [[1j7b]], [[1j7c]] , [[1qoa]], [[1qob]], [[1qof]], [[1qog]]- aFd (mutant)
**** [[1e0z]] – Fd – Halobacterium salinarium
**** [[1pfd]] – Fd – Petroselinum crispum – NMR
**** [[1a70]] - Fd (mutant) – Spinacia oleracea
**** [[1awd]] - Fd – Chlorella fusca
**** [[2cjn]], [[2cjo]], [[1roe]] – SyFd – NMR
**** [[1rof]] – SyFd – Synechococcus elongates
**** [[1doi]] - Fd – Haloarcula marismortui
**** [[4fxc]] – Fd – Spirulina platensis
**** [[1fxi]] – Fd – Aphanothece sacrum
**** [[3dqy]], [[2qpz]] - Fd – Pseudomonas putida

*** 4Fe-4S containing ferredoxins

**** [[3eun]] – AvFd – Allochromatium vinosum
**** [[3exy]] - AvFd (mutant)
**** [[2vkr]] - Fd+Zn – Acidianus ambivalens
**** [[2z8q]] - PfFd (mutant) – Pyrococcus furiosus
**** [[2fgo]] - Fd– Pseudomonas aeruginosa
**** [[1iqz]], [[1ir0]] - BtFd – Bacillus thermoproteolyticus
**** [[1rgv]] - Fd – Thauera aromatica
**** [[1dax]], [[1dfd]] – DaFd – Desulfovibrio africanus – NMR
**** [[1fxr]] - DaFd
**** [[1vjw]] – Fd – Thermotoga maritima

*** 3Fe-4S containing ferredoxins

**** [[2v2k]] – Fd – Mycobacterium smegmatis
**** [[1wtf]] - BtFd (mutant)
**** [[1sj1]] - PfFd
**** [[1fxd]] - DgFd – Desulfovibrio gigas
**** [[1f2g]] – DgFd – NMR
**** [[1xer]] - Fd – Sulfolobus tokodaii

*** 4Fe-4S+3Fe-4S containing ferredoxins

**** [[1gao]], [[6fdr]], [[7fd1]], [[7fdr]], [[1axq]], [[6fd1]], [[1frh]], **** [[1fri]],[[1frj]], [[1frk]], [[1frl]], [[1frm]], [[1fda]], [[1fdb]], **** [[1fdd]], [[5fd1]], [[1fer]] – AvFd – Azotobacter vinelandii
**** [[1pc4]], [[1pc5]], [[1g6b]], [[1g3o]], [[1ff2]], [[1b0v]], [[1d3w]], **** [[1b0t]], [[1a6l]], [[1ftc]], [[1frx]], [[2fd2]], [[1fd2]] - AvFd (mutant)
**** [[1h98]] – Fd – Thermus thermophilus
**** [[1a8p]], [[1bd6]] - BsFd – Bacillus schlegelii – NMR

*** 4Fe-4S+4Fe-4S containing ferredoxins

**** [[1dur]] – Fd – Peptoniphilus asaccarolyticus
**** [[1bwe]], [[1bqx]] - BsFd (mutant) – NMR
**** [[2fdn]], [[1fca]] , [[1fdn]]- Fd – Clostridium acidi-urici
**** [[1blu]] - Fd – Chromatium vinosum
**** [[1clf ]]– Fd – Clostridium pasteurianum – NMR

*** Adrenoredoxin

**** [[2jqr]] – ADR Fd domain (mutant)+cytochrome c (mutant) – yeast – NMR
**** [[2bt6]] – cADR1 modified – cow
**** [[1l6u]], [[1l6v]] – cADR1 – NMR
**** [[1e6e]] – cADR (mutant)+ADR reductase
**** [[1cje]], [[1ayf]] - cADR

*** Putidaredoxin

**** [[1yji]], [[1yjj]], [[1pdx]] – PpPUT – Pseudomonas putida – NMR
**** [[3lb8]] – PpPUT (mutant)+PUT reductase
**** [[1xln]], [[1xlo]], [[1xlp]], [[1xlq]], [[1r7s]], [[1oqq]], [[1oqr]] - PpPUT (mutant)
**** [[1gpx]], [[1put]]- PpPUT (mutant) - NMR

*** Terpredoxin

**** [[1b9r]] – TER – Pseudomonas - NMR

* Toxins
** [[Pore forming toxin, α-hemolsyin|The pore forming toxin, α-hemolsyin]]
** [[Insecticidal delta-endotoxin Cyt2Ba from Bacillus thuringiensis]]

* Diseases
** Cancer
*** [[SRC]]
*** [[Proteins involved in cancer]]

* Evolution
** [[Conservation, Evolutionary]]
** [[Extremophiles]]

* Gene Expression and Replication
** Nucleic Acid Structure
*** [[DNA]]
**** B-DNA [[1bna]]
**** [[Z-DNA]]
*** [[Nucleosomes]]

** DNA Replication, Repair, and Recombination
*** [[DNA Replication,Transcription and Translation]]
*** [[DNA Polymerase I]]
*** [[PcrA helicase]]
*** [[Fpg Nei Protein Superfamily]] - DNA Repair and Base Excision DNA Repair
*** [[Human RecQ-Like protein 1]] - RecQ family of DNA helicases are conserved in from bacteria to man
*** [[Structure of E. coli DnaC helicase loader]]
*** [[1x9n#Crystal Structure of Human DNA Ligase I bound to 5.27-adenylated.2C nicked DNA]]
*** [[Rop protein]]

** Transcription and RNA Processing
*** T-box family
**** [[T-box proteins]]
**** [[T]]
*** [[C-Myc]]
*** [[Lac repressor]]
*** [[Reverse transcriptase]]
*** [[TATA-Binding Protein]]
*** [[RSP1275]]
*** [[Transcription Termination Factor Rho]]

** Protein Synthesis
*** [[Ribosome]]
*** [[Large Ribosomal Subunit of Haloarcula|Large Ribosomal Subunit]]
*** [[SelB Recognition]]
** Regulation of Gene Expression
*** [[Lac repressor]]
*** [[Irr]] (Iron Response Regulator )
*** Oncogenes
**** [[P53]]
**** [[SRC]]
*** [[Tangible Models of Cdc42 Interacting With Intersectin]]

* Immune System
** Antibodies
*** [[IgA]]
*** [[Epitopes]]
** [[Major Histocompatibility Complex Class I]]
*** [[Human beta two microglobulin]]

* Metabolism
** Introduction to Metabolism

** Glucose Catabolism
*** [[Triose Phosphate Isomerase]]
***[[Phosphofructokinase %28PFK%29]]

** Glycogen Metabolism and Gluconeogenesis
*** [[Phosphoglucose isomerase]]
*** [[Calmodulin in motion]]
*** [[Biotin Protein Ligase]]

** Citric Acid Cycle
*** [[Aconitase]]

** Electron Transport and Oxidative Phosphorylation
*** [[NADH quinone oxidoreductase ]]

** Photosynthesis
*** [[Photosystem II]]
*** [[Ribulose-1,5-bisphosphate carboxylase/oxygenase]]
*** [[PrrA in Rhodobacter sphaeroides]]
*** [[Pyruvate phosphate dikinase]]

** Lipid Metabolism
*** [[Acid-beta-glucosidase]]
** Amino Acid Metabolism
*** [[Aromatic amino acid hydroxylases]]
*** [[Phenylalanine hydroxylase]]
*** [[Tyrosine hydroxylase]]
*** [[ATP Phosphoribosyl Transferase]]
*** [[Isochorismate pyruvate lyase]]
** Mammalian Fuel Metabolism: Integration and Regulation
** Nucleotide Metabolism
*** [[Dihydrofolate reductase]]

* Methods of Structure Determination
** X-ray
*** [[X-ray crystallography]]
**** [[Asymmetric Unit]]
**** [[Biological Unit]]
**** [[Electron density maps]]
*** SAXS
** NMR
*** [[NMR Ensembles of Models]]
** Electron Microscopy

* Methods of Structure & Sequence Analysis
** Structural Analysis & Visualization
*** [[CPK]] - Corey-Pauling-Koltun spacefilling molecular models and color scheme for elements
*** [[Chime]]
*** Jmol
**** [[S347/Visualising protein structure|Visualising Protein Structure]] - Introduction to Jmol
**** [[FirstGlance in Jmol]]
*** [[User:Wayne Decatur/Teaching Proteopedia|Teaching Proteopedia]]
*** [[User:Wayne Decatur/Generate Unfolded Structures|Generate Unfolded Structures]]
*** Homology Model
**** [[User:Wayne Decatur/Homology Modeling|Homology Modeling]]
**** [[User:Emi Nakayama/TRIM5a Homology Models|TRIM5a Homology Models]] - Differences in models as a function of their templates
*** [[DRuMS]] - set of standard color schemes for macromolecular visualization

** Sequence Analysis
*** [[User:Wayne Decatur/Sequence analysis tools|Sequence Analysis Tools]]

* Model Structures
** See [[Theoretical models]]
** [[African Malaria Mosquito Acetylcholinesterase]]
** [[Structure of E. coli DnaC helicase loader]]
** [[User:Yuan-Ping Pang/HAB•BoNTAe]]

* Miscellaneous
** [[Molecular Playground]]
** [[Research Groups]]
}}
</big>

T-box proteins

2010-07-06T18:16:47Z

Helen Ginn:

[[Image:TBX3.png|thumb|right|alt=TBX3 dimer on DNA|TBX3, a T-box protein, binds to palindromic DNA as a dimer.]]

=Introduction=

The family of T-box proteins are transcription factors with a transcriptional activator or repressor domain and a DNA-binding T-box domain. The first two proteins discovered were Brachyury and Omb, which were found to have a new distinct domain unlike any other, designated the T-box domain. Other homologous proteins have been discovered in both invertebrate and vertebrate organisms but not in some organisms such as ''Aribidopsis thaliana''. This family has ~20 members in ''Homo sapiens''.

=Gene loci and structure=

The loci of these genes are dispersed throughout the genomes of relevant oragnisms, though a few select cases of clustering exist. Tight linkages include Tbx8 and Tbx9 in ''C. elegans'', and in mice: Tbx2 and Tbx4 on chromosome 11; and Tbx3 and Tbx5 on chromosome 5. Similar linkages are present in humans. These genes include multiple exons, typically 8 (as in Tbx5). There are a few cases of alternative splicing, such as VegT in ''Xenopus'' and [[TBX1]] in humans.

=Protein structure=

A T-box protein is typically 50 - 78 kDa, within which the T-box domain is typically 17 - 26 kDa. T-box proteins have folds characteristic of the immunoglobin fold. The T-box domains of most family members bind to the consensus sequence TCACACCT. Some residues are conserved through particular subfamilies, such as Lys149 of the Xbra family, and others throughout the entire T-box family. However, differences lie in the binding topology of multiple recognised sequence motifs. For example, Xbra binds two head-to-head sequence motifs, and cannot bind them tail-to-tail; VegT can bind tail-to-tail and not head-to-head. It has been suggested that other functions may lie within the T-box such as mediating protein-protein interactions. The transcription-mediating domain can either be activating or repressing and bears less to no sequence homology.

=Function and implications in development=

T-box proteins are expressed in specific organs or in only particular cell types, and are involved in decisions about early cell fate. Mutant alleles typically show haploinsufficiency (T-box proteins tend to be dosage-specific). When mutations occur, developmental disorders arise such as the ulnar-mammary syndrome caused by mutations in TBX3, and some aspects of DiGeorge syndrome implicated by mutations in TBX1.

Genes involved in limb bud formation and development are a subset of T-box proteins: [[T]], TBX2, [[TBX3]], [[TBX5]], [[TBX15]] and TBX18.

=T-box family members in ''Homo sapiens''=

{| class="wikitable" style="width: 90%;"
|+ T subfamily
! Members
! Notes
! Linked diseases
|-
| [[T]]
| Crystal structure solved
|
|-
| TBX19
|
|
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX1 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX1
| Crystal structure solved
| DiGeorge syndrome
|-
| TBX10
|
|
|-
| TBX15
|
| Cousin syndrome
|-
| TBX18
|
|
|-
| TBX20
|
|
|-
| TBX22
| Truncated T-box domain predicted not to bind DNA
| Cleft palate with ankyloglossia
|-
|}

{| class="wikitable" style="width: 90%;"
|+ TBX2 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX2
| Mutation of Arg122 destroys DNA binding. Acts as a repressor. TRP-1 promoter is a possible binding site.
| Amplified in certain types of breast cancer.
|-
| TBX3
| Crystal structure solved
| Ulnar-mammary syndrome
|-
| TBX4
|
| Small patella syndrome
|-
| TBX5
|
| Holt-Oram syndrome
|}

{| class="wikitable" style="width: 90%;"
|+ TBX6 subfamily
! Members
! Notes
! Linked diseases
|-
| TBX6
|
|
|-
| MGA
| Also contains leucine zipper domain
|
|}

{| class="wikitable" style="width: 90%;"
|+ TBR subfamily
! Members
! Notes
! Linked diseases
|-
| TBR1
|
|
|-
| EOMES
|
|
|-
| TBX21
|
|
|}