PDBsum entry 5cve

Transferase/peptide

PDB id: 5cve

Contents

Protein chains

231 a.a.

Ligands

PBE-PRO-LYS-THR-SER-GLY-LYS-ALA

PBE-PRO-LYS-THR-SER-GLY

SAH ×2

Waters ×754

PDB id:

5cve

Name:

Transferase/peptide

Title:

Crystal structure of human nrmt1 in complex with dimethylated fly h2b peptide and sah

Structure:

N-terminal xaa-pro-lys n-methyltransferase 1. Chain: a, b. Synonym: alpha n-terminal protein methyltransferase 1a, methyltransferase-like protein 11a,n-terminal rcc1 methyltransferase, x-pro-lys n-terminal protein methyltransferase 1a,ntm1a. Engineered: yes. N-terminal peptide from histone h2b. Chain: d, e. Fragment: unp residues 2-10.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ntmt1,nrmt1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Drosophila melanogaster. Fruit fly.

Resolution:

1.50Å R-factor: 0.153 R-free: 0.180

Authors:

R.Wu,H.Li

Key ref:

R.Wu et al. (2015). Molecular basis for histone N-terminal methylation by NRMT1. Genes Dev, 29, 2337-2342. PubMed id: 26543159 DOI: 10.1101/gad.270926.115

Date:

26-Jul-15 Release date: 25-Nov-15

Protein chains

Q9BV86  (NTM1A_HUMAN) -  N-terminal Xaa-Pro-Lys N-methyltransferase 1 from Homo sapiens

Seq: 223 a.a.

Struc: 231 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.244 - protein N-terminal methyltransferase.
• Reaction:
  1. N-terminal L-alanyl-L-prolyl-L-lysyl-[protein] + 3 S-adenosyl-L- methionine = N-terminal N,N,N-trimethyl-L-alanyl-L-prolyl-L-lysyl- [protein] + 3 S-adenosyl-L-homocysteine + 3 H⁺
  2. N-terminal L-seryl-L-prolyl-L-lysyl-[protein] + 3 S-adenosyl-L- methionine = N-terminal N,N,N-trimethyl-L-seryl-L-prolyl-L-lysyl- [protein] + 3 S-adenosyl-L-homocysteine + 3 H⁺
  3. N-terminal L-prolyl-L-prolyl-L-lysyl-[protein] + 2 S-adenosyl-L- methionine = N-terminal N,N-dimethyl-L-prolyl-L-prolyl-L-lysyl-[protein] + 2 S-adenosyl-L-homocysteine + 2 H⁺

N-terminal L-alanyl-L-prolyl-L-lysyl-[protein] + 3 × S-adenosyl-L- methionine = N-terminal N,N,N-trimethyl-L-alanyl-L-prolyl-L-lysyl- [protein] + 3 × S-adenosyl-L-homocysteine (Bound ligand (Het Group name = SAH) corresponds exactly) + 3 × H(+)

N-terminal L-seryl-L-prolyl-L-lysyl-[protein] + 3 × S-adenosyl-L- methionine = N-terminal N,N,N-trimethyl-L-seryl-L-prolyl-L-lysyl- [protein] + 3 × S-adenosyl-L-homocysteine (Bound ligand (Het Group name = SAH) corresponds exactly) + 3 × H(+)

N-terminal L-prolyl-L-prolyl-L-lysyl-[protein] + 2 × S-adenosyl-L- methionine = N-terminal N,N-dimethyl-L-prolyl-L-prolyl-L-lysyl-[protein] + 2 × S-adenosyl-L-homocysteine (Bound ligand (Het Group name = SAH) corresponds exactly) + 2 × H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1101/gad.270926.115

Genes Dev 29:2337-2342 (2015)

PubMed id: 26543159

Molecular basis for histone N-terminal methylation by NRMT1.

R.Wu, Y.Yue, X.Zheng, H.Li.

ABSTRACT

NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates. Here, we report the crystal structure of human NRMT1 bound to CENP-A peptide at 1.3 Å. NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases. Key substrate recognition and catalytic residues were identified by mutagenesis studies. Histone peptide profiling revealed that human NRMT1 is highly selective to human CENP-A and fruit fly H2B, which share a common "Xaa-Pro-Lys/Arg" motif. These results, along with a 1.5 Å costructure of human NRMT1 bound to the fruit fly H2B peptide, underscore the importance of the NRMT1 recognition motif.