PDBsum entry 4n6m

Hydrolase inhibitor

PDB id: 4n6m

Contents

Protein chains

117 a.a.

Ligands

SO4

Waters ×29

PDB id:

4n6m

Name:

Hydrolase inhibitor

Title:

Crystal structure of human cystatin e/m produced in lexsy

Structure:

Cystatin-m. Chain: a, b. Fragment: unp residues 29-149. Synonym: cystatin-6, cystatin-e. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cst6. Expressed in: leishmania tarentolae. Expression_system_taxid: 5689.

Resolution:

2.90Å R-factor: 0.261 R-free: 0.283

Authors:

E.Dall,H.Brandstetter

Key ref:

E.Dall et al. (2015). Structure and mechanism of an aspartimide-dependent peptide ligase in human legumain. Angew Chem Int Ed Engl, 54, 2917-2921. PubMed id: 25630877 DOI: 10.1002/anie.201409135

Date:

14-Oct-13 Release date: 18-Feb-15

Protein chains

Q15828  (CYTM_HUMAN) -  Cystatin-M from Homo sapiens

Seq: 149 a.a.

Struc: 117 a.a.

DOI no: 10.1002/anie.201409135

Angew Chem Int Ed Engl 54:2917-2921 (2015)

PubMed id: 25630877

Structure and mechanism of an aspartimide-dependent peptide ligase in human legumain.

E.Dall, J.C.Fegg, P.Briza, H.Brandstetter.

ABSTRACT

Peptide ligases expand the repertoire of genetically encoded protein architectures by synthesizing new peptide bonds, energetically driven by ATP or NTPs. Here, we report the discovery of a genuine ligase activity in human legumain (AEP) which has important roles in immunity and tumor progression that were believed to be due to its established cysteine protease activity. Defying dogma, the ligase reaction is independent of the catalytic cysteine but exploits an endogenous energy reservoir that results from the conversion of a conserved aspartate to a metastable aspartimide. Legumain's dual protease-ligase activities are pH- and thus localization controlled, dominating at acidic and neutral pH, respectively. Their relevance includes reversible on-off switching of cystatin inhibitors and enzyme (in)activation, and may affect the generation of three-dimensional MHC epitopes. The aspartate-aspartimide (succinimide) pair represents a new paradigm of coupling endergonic reactions in ATP-scarce environments.