Modomics - A Database of RNA Modifications

ID Card:

Full name: U8 snoRNA-decapping enzyme
GI: 68565926
UniProt: Q96DE0
Structures: | 2XSQ | 3COU | 3MGM | 5VY2 | 5W6X | 5W6Z | 5WJI | 6B09 | 6C02 | 6X7U | 6X7V |
Alpha Fold Predicted Structure: AF-Q96DE0-F1
Enzyme type: hydrolase


PDB Structures:


2XSQ

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Human NUDT16 is a member of the NUDIX hydrolase superfamily. After having been initially described as an mRNA decapping enzyme, recent studies conferred it a role as an "housecleaning" enzyme specialized in the removal of hazardous (deoxy)inosine diphosphate from the nucleotide pool. Here we present the crystal structure of human NUDT16 both in its apo-form and in complex with its product inosine monophosphate (IMP). NUDT16 appears as a dimer whose formation generates a positively charged trench to accommodate substrate-binding. Complementation of the structural data with detailed enzymatic and biophysical studies revealed the determinants of substrate recognition and particularly the importance of the substituents in position 2 and 6 on the purine ring. The affinity for the IMP product, harboring a carbonyl in position 6 on the base, compared to purine monophosphates lacking a H-bond acceptor in this position, implies a catalytic cycle whose rate is primarily regulated by the product-release step. Finally, we have also characterized a phenomenon of inhibition by the product of the reaction, IMP, which might exclude non-deleterious nucleotides from NUDT16-mediated hydrolysis regardless of their cellular concentration. Taken together, this study details structural and regulatory mechanisms explaining how substrates are selected for hydrolysis by human NUDT16.

Download RCSB-PDB Structures:

Pdb Files   2XSQ.pdb   3COU.pdb   3MGM.pdb   5VY2.pdb   5W6X.pdb   5W6Z.pdb   5WJI.pdb   6B09.pdb   6C02.pdb   6X7U.pdb   6X7V.pdb  
Pdbx/mmCIF Files   2XSQ.cif   3COU.cif   3MGM.cif   5VY2.cif   5W6X.cif   5W6Z.cif   5WJI.cif   6B09.cif   6C02.cif   6X7U.cif   6X7V.cif  


Protein sequence:

MAGARRLELGEALALGSGWRHACHALLYAPDPGMLFGRIPLRYAILMQMRFDGRLGFPGGFVDTQDRSLEDGLNRELREELGEAAAAFRVERTDYRSSHVGSGPRVVAHFYAKRLTLEELLAVEAGATRAKDHGLEVLGLVRVPLYTLRDGVGGLPTFLENSFIGSAREQLLEALQDLGLLQSGSISGLKIPAHH

Comments:

RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Part of the U8 snoRNP complex that is required for the accumulation of mature 5.8S and 28S rRNA. Has diphosphatase activity and removes m7G and/or m227G caps from U8 snoRNA and leaves a 5'monophosphate on the RNA. Catalyzes also the cleavage of the cap structure on mRNAs. Does not hydrolyze cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG). Also hydrolysis m7G- and m227G U3-capped RNAs but with less efficiencies. Has broad substrate specificity with manganese or cobalt as cofactor and can act on various RNA species. Binds to the U8 snoRNA; metal is not required for RNA-binding. May play a role in the regulation of snoRNAs and mRNAs degradation. Acts also as a phosphatase; hydrolyzes the non-canonical purine nucleotides inosine diphosphate (IDP) and deoxyinosine diphosphate (dITP) as well as guanosine diphosphate (GDP), deoxyguanosine diphosphate (dGDP), xanthine diphosphate (XDP), inosine triphosphate (ITP) and deoxyinosine triphosphate (ITP) to their respective monophosphate derivatives and does not distinguish between the deoxy- and ribose forms (PubMed:20385596, PubMed:26121039).





Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-Q96DE0-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q96DE0-F1.cif  
DSSP Secondary Structures   Q96DE0.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI