Modomics - A Database of RNA Modifications

ID Card:

Full name: RNA demethylase ALKBH5
Synonym: ABH5, OFOXD1
GI: 148539642
UniProt: Q6P6C2
Structures: | 4NRM | 4NRP | 4NRQ | 4NRO | 4O7X | 7WKV | 7WL0 | 4OCT | 4NPL | 4NPM | 7V4G | 4O61 | 4NJ4 | 4QKN | 4NID | 4NIG | 4NII | 4NIH |
Alpha Fold Predicted Structure: AF-Q6P6C2-F1
Enzyme type: demethylase
Position of modification - modification: m:many - A


PDB Structures:


4NRM

Structure Description:

Title: Crystal structure of AlkB D135I/E136H mutant protein with cofactors bound to dsDNA containing m6A/A
Classification: OXIDOREDUCTASE/DNA
Technique: X-Ray Diffraction
Resolution: 1.52
R value free: 0.212
R value observed: 1.81
R value work: 1.80

Abstract of the PDB Structure's related Publication:

The AlkB family demethylases AlkB, FTO, and ALKBH5 recognize differentially methylated RNA/DNA substrates, which results in their distinct biological roles. Here we identify key active-site residues that contribute to their substrate specificity. Swapping such active-site residues between the demethylases leads to partially switched demethylation activities. Combined evidence from X-ray structures and enzyme kinetics suggests a role of the active-site residues in substrate recognition. Such a divergent active-site sequence may aid the design of selective inhibitors that can discriminate these homologue RNA/DNA demethylases.

Download RCSB-PDB Structures:

Pdb Files   4NIG.pdb   4NII.pdb   4NJ4.pdb   4NPL.pdb   4NPM.pdb   4NRM.pdb   4NRO.pdb   4NRP.pdb   4NRQ.pdb   4O61.pdb   4O7X.pdb   4OCT.pdb   4QKN.pdb   7V4G.pdb   7WKV.pdb   7WL0.pdb  
Pdbx/mmCIF Files   4NIG.cif   4NII.cif   4NJ4.cif   4NPL.cif   4NPM.cif   4NRM.cif   4NRO.cif   4NRP.cif   4NRQ.cif   4O61.cif   4O7X.cif   4OCT.cif   4QKN.cif   7V4G.cif   7WKV.cif   7WL0.cif  


Protein sequence:

MAAASGYTDLREKLKSMTSRDNYKAGSREAAAAAAAAVAAAAAAAAAAEPYPVSGAKRKYQEDSDPERSDYEEQQLQKEEEARKVKSGIRQMRLFSQDECAKIEARIDEVVSRAEKGLYNEHTVDRAPLRNKYFFGEGYTYGAQLQKRGPGQERLYPPGDVDEIPEWVHQLVIQKLVEHRVIPEGFVNSAVINDYQPGGCIVSHVDPIHIFERPIVSVSFFSDSALCFGCKFQFKPIRVSEPVLSLPVRRGSVTVLSGYAADEITHCIRPQDIKERRAVIILRKTRLDAPRLETKSLSSSVLPPSYASDRLSGNNRDPALKPKRSHRKADPDAAHRPRILEMDKEENRRSVLLPTHRRRGSFSSENYWRKSYESSEDCSEAAGSPARKVKMRRH

Comments:

Belongs to AlkB family of nonheme Fe(II)/a-ketoglutarate (a-KG)-dependent dioxygenases (same protein family as FTO demethylase). In vitro demethylates m6A in RNA and DNA however m6A in mRNA is a physiologically relevant substrate of ALKBH5 inside cells. Strongly prefers single-stranded substrates, exhibits an almost unnoticeable demethylation activity toward m6A in a 26-mer double-stranded RNA. ALKBH5 and its demethylation activity play important roles in mRNA export as well as roles in the association of the nuclear speckle proteins and RNA metabolism. The Alkbh5 deficiency leads to aberrant spermatogenesis and apoptosis in mouse testes. Transcriptome analysis revealed differentially expressed genes associated with spermatogenesis and the p53 functional interaction network, in line with the impaired fertility observed for the Alkbh5-/- mouse.





Alpha Fold Predicted Structure:




Downloading... [204538/361653]


Clear Selection and Reset Camera

Protein sequence:

M A A A S G Y T D L R E K L K S M T S R D N Y K A G S R E A A A A A A A A V A A A A A A A A A A E P Y P V S G A K R K Y Q E D S D P E R S D Y E E Q Q L Q K E E E A R K V K S G I R Q M R L F S Q D E C A K I E A R I D E V V S R A E K G L Y N E H T V D R A P L R N K Y F F G E G Y T Y G A Q L Q K R G P G Q E R L Y P P G D V D E I P E W V H Q L V I Q K L V E H R V I P E G F V N S A V I N D Y Q P G G C I V S H V D P I H I F E R P I V S V S F F S D S A L C F G C K F Q F K P I R V S E P V L S L P V R R G S V T V L S G Y A A D E I T H C I R P Q D I K E R R A V I I L R K T R L D A P R L E T K S L S S S V L P P S Y A S D R L S G N N R D P A L K P K R S H R K A D P D A A H R P R I L E M D K E E N R R S V L L P T H R R R G S F S S E N Y W R K S Y E S S E D C S E A A G S P A R K V K M R R H
50100150200250300350SequenceGHITBSN

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-Q6P6C2-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q6P6C2-F1.cif  
DSSP Secondary Structures   Q6P6C2.dssp  





Diseases connected to this enzyme:

Publications:

Links:

_PubMed_