Comparison of two 3D structures obtained by
X-ray scattering taking into account the presence and absence of the DNA TATA box

TAF4-T2AG-CH3.

DNA TATA-Box and DNA without TATA-Box

Исследования сравнения влияния присутствия и отсутствия ТАТА-бокса ДНК на аффинность связывания с факторами транскрипции, а так же при различных мутациях при различных онкологических заболеваниях из Cancer Research Atlas.

Ниже приведены описание и перечень таких мутаций для выбранных белков GTF2A2 and TAF4, для которых будет выполнен расчет связывания с ДНК с учетом наличия и отсутствия ТАТА-бокса. Сравнение и наложение структур так же приведены ниже.
Symbol: GTF2A2
Name: general transcription factor IIA, 2, 12kDa
Synonyms: HsT18745
_________ TFIIA
AA change: L15F
¹ of Case:1/-
Desease type: cystic,
mucinous and serous
neoplasm
AA change: E21V
¹ of Case:1-
Desease type:
plasma cell tumors
AA change: S25T
¹ of Case:1/alive
Desease type:nevi and
melanomas
AA change: Q35E
¹ of Case:1/-
Desease type:
ductal and lobular
neoplasm
AA change: F67L
¹ of Case:1/0
Desease type:
adenomas and
adenocarcinomas,
AA change: C68F
¹ of Case:1/alive
Desease type:squamous cell
neoplasms
AA change: D68N
¹ of Case:1/alive
Desease type:squamous cell
neoplasms
AA change: N77H
¹ of Case:1/0
Desease type:
adenomas and
adenocarcinomas
Symbol:TAF4
Name: TAF4 RNA polymerase II, TATA box binding protein
(TBP)-associated factor, 135kDa
Synonyms:TAF2C
_______________TAF2C1
_______________TAF4A
_______________TAFII130
_______________TAFII135

AA change: P877H
№ of Case:1/0
Desease type:
adenomas and
adenocarcinomas
AA change: P877L
№ of Case:0/1
Desease type: nev
and melanomas
AA change: I882V
№ of Case:1/0
Desease type:
adenomas and
adenocarcinomas
AA change: V898L
№ of Case:1/0
Desease type:
transitional cell papillomas
adn carcinomas
AA change: V899L
№ of Case:1/-
Desease type: cystic,
mucinous and serous
neoplasm
AA change: E915D
№ of Case:2/0
Desease type: epithelial
neoplasms,
adenomas and
adenocarcinomas
AA change: K924N
№ of Case:2/0
Desease type: transitional
cell papillomas
and carcinomas,
adenomas and
adenocarcinomas
AA change: D932N
№ of Case:2/0
Desease type:cystic,
mucinous and serous
neoplasm,
adenomas and
adenocarcinomas
AA change: Q961E
№ of Case:0/1
Desease type:
squamous cell
neoplasms
AA change: D978N
№ of Case:0/1
Desease type: cystic,
mucinous and serous
neoplasm
AA change: Q998H
№ of Case:1/0
Desease type:
adenomas and
adenocarcinomas,
AA change: S1041R
№ of Case:0/1
Desease type:
adenomas and
adenocarcinomas
AA change: T1046P
№ of Case:1/0
Desease type:
adenomas and
adenocarcinomas
AA change: R1057Q
№ of Case:2/0
Desease type: cystic,
mucinous and serous
neoplasm,
adenomas and
adenocarcinomas
AA change: L1060P
№ of Case:1/0
Desease type: cystic,
mucinous and serous
neoplasm
AA change: S1042L
№ of Case:0/1
Desease type: cystic,
mucinous and serous
neoplasm
AA change: E1072Q
№ of Case:0/1
Desease type:
adenomas and
adenocarcinomas
Mutations have been identified
that are in the region of
interacting polypeptide
chains during trimer formation
TAF4-T2AG-CH3
for two different structures: the presence of a DNA TATA box and the absence of a DNA TATA box
The structure of the trimer indicating the substitutions of amino acid residues in proteins
Difference in three-dimensional structures considering the presence and absence of the
DNA TATA box
Figure. 5. Structural overlay. visual comparison of three-dimensional structures 7edx and 7eg8.
As can be seen, the dimers coincide almost up to a couple of angstrems, however, the TAF4 alpha helix clearly has a different degree of immersion in the beta structures of the dimer.
Desease type:squamous cell
neoplasms.
This substitution significantly changes the affinity of the trimeric complex compared to the other substitutions performed.
Desease type:squamous cell
neoplasms.
This substitution significantly changes the affinity of the trimeric complex compared to the other substitutions performed.
PDB:7edx
PDB:7edx
PDB:7ed8
PDB:7ed8
PDB:7edx
PDB:7ed8
GTF2A2 PDB:7edx
TAF4 PDB:7edx
Figure 1.Dependence of RMSD(root-mean-square deviation) on the configuration number
Figure 2.Dependence of RMSD(root-mean-square deviation) on the configuration number
If an optimized cost function H for a specific PDB structure is found, then we consider that this structure is formed correctly and the following calculations are issued to find the local minimum. If an optimized cost function for a specific PDB structure is not found, then we consider that this structure is formed incorrectly, Fig.1-2.
Figure 3. Structure of biocomplex with
TATA-box.
Figure 4. Comparison of Structures with TATA-box and without TATA-box.
Table 1.
Figure 6. Calculation results for two different structures, taking into account the involved proteins.
Figure 7. List of file names for calculations used in the program.
AA change: Q998H
№ of Case:1/0
Desease type:
adenomas and
adenocarcinomas,
Symbol: GTF2A2
Name: general transcription factor IIA, 2, 12kDa
Synonyms: HsT18745
TFIIA
Symbol:TAF4
Name:TAF4 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 135kDa
Synonyms:TAF2C
_______________TAF2C1
_______________TAF4A
_______________TAFII130
_______________TAFII135

AA change: C68F
¹ of Case:1/alive
Desease type:squamous cell
neoplasms
AA change: F67L
¹ of Case:1/0
Desease type:
adenomas and
adenocarcinomas,
AA change: Q35E
¹ of Case:1/-
Desease type:
ductal and lobular
neoplasm
TAF4 (TATA box structure)
PDB:7eg8 TATA-box
error computational SVD
1.385e-19
max eigenvalue min eigenvalue
1.6405e-19_________4.2642e-23
number condition
3.5853
PDB:7edx without TATA-box
error computational SVD
1.3374e-19
max eigenvalue min eigenvalue
1.6511e-19_________3.568e-23
number condition
3.66528
Dependence of RMSD(root-mean-square deviation) on the configuration number.
Determination of the computational error of the SVD
Comparison of calculation results among themselves.
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