PDBsum entry 7d1h

Transferase

PDB id: 7d1h

Contents

Protein chain

326 a.a.

Metals

_ZN

Waters ×356

PDB id:

7d1h

Name:

Transferase

Title:

Crystal structure of ixodes scapularis glutaminyl cyclase with d238a mutation

Structure:

Glutaminyl-peptide cyclotransferase. Chain: a. Engineered: yes

Source:

Ixodes scapularis. Black-legged tick. Organism_taxid: 6945. Gene: 8042451, iscw_iscw023264. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.69Å R-factor: 0.185 R-free: 0.218

Authors:

K.-F.Huang,J.-S.Huang,M.-L.Wu,W.-L.Hsieh,A.H.-J.Wang

Key ref:

K.F.Huang et al. (2021). A Unique Carboxylic-Acid Hydrogen-Bond Network (CAHBN) Confers Glutaminyl Cyclase Activity on M28 Family Enzymes. J Mol Biol, 433, 166960. PubMed id: 33774034 DOI: 10.1016/j.jmb.2021.166960

Date:

14-Sep-20 Release date: 14-Apr-21

Protein chain

B7QK46  (B7QK46_IXOSC) -  Glutaminyl-peptide cyclotransferase from Ixodes scapularis

Seq: 353 a.a.

Struc: 326 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.5 - glutaminyl-peptide cyclotransferase.
• Reaction: N-terminal L-glutaminyl-[peptide] = N-terminal 5-oxo-L-prolyl-[peptide] + NH4⁺

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

Added reference

DOI no: 10.1016/j.jmb.2021.166960

J Mol Biol 433:166960 (2021)

PubMed id: 33774034

A Unique Carboxylic-Acid Hydrogen-Bond Network (CAHBN) Confers Glutaminyl Cyclase Activity on M28 Family Enzymes.

K.F.Huang, J.S.Huang, M.L.Wu, W.L.Hsieh, K.C.Hsu, H.L.Hsu, T.P.Ko, A.H.Wang.

ABSTRACT

Proteins with sequence or structure similar to those of di-Zn exopeptidases are usually classified as the M28-family enzymes, including the mammalian-type glutaminyl cyclases (QCs). QC catalyzes protein N-terminal pyroglutamate formation, a posttranslational modification important under many physiological and pathological conditions, and is a drug target for treating neurodegenerative diseases, cancers and inflammatory disorders. Without functional characterization, mammalian QCs and their orthologs remain indistinguishable at the sequence and structure levels from other M28-family proteins, leading to few reported QCs. Here, we show that a low-barrier carboxylic-acid hydrogen-bond network (CAHBN) is required for QC activity and discriminates QCs from M28-family peptidases. We demonstrate that the CAHBN-containing M28 peptidases deposited in the PDB are indeed QCs. Our analyses identify several thousands of QCs from the three domains of life, and we enzymatically and structurally characterize several. For the first time, the interplay between a CAHBN and the binuclear metal-binding center of mammalian QCs is made clear. We found that the presence or absence of CAHBN is a key discriminator for the formation of either the mono-Zn QCs or the di-Zn exopeptidases. Our study helps explain the possible roles of QCs in life.