PDBsum entry 7d1d

Transferase

PDB id: 7d1d

Contents

Protein chain

294 a.a.

Ligands

1BN

Metals

_ZN

Waters ×218

PDB id:

7d1d

Name:

Transferase

Title:

Crystal structure of bacteroides thetaiotaomicron glutaminyl cyclase bound to 1-benzylimidazole

Structure:

Glutamine cyclotransferase. Chain: a. Engineered: yes

Source:

Bacteroides thetaiotaomicron. Organism_taxid: 818. Gene: batf92_38840. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.75Å R-factor: 0.135 R-free: 0.180

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

Q8A4P9  (Q8A4P9_BACTN) -  Leucine aminopeptidase from Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / JCM 5827 / CCUG 10774 / NCTC 10582 / VPI-5482 / E50)

Seq: 331 a.a.

Struc: 294 a.a.

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.