6ZPT

Crystal structure of the open conformation of S2_S'-mutant human Angiotensin-1 converting enzyme N-domain.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.225 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Angiotensin-converting enzyme open for business: structural insights into the subdomain dynamics.

Cozier, G.E.Lubbe, L.Sturrock, E.D.Acharya, K.R.

(2021) FEBS J 288: 2238-2256

  • DOI: https://doi.org/10.1111/febs.15601
  • Primary Citation of Related Structures:  
    6ZPQ, 6ZPT, 6ZPU

  • PubMed Abstract: 

    Angiotensin-1-converting enzyme (ACE) is a key enzyme in the renin-angiotensin-aldosterone and kinin systems where it cleaves angiotensin I and bradykinin peptides, respectively. However, ACE also participates in numerous other physiological functions, can hydrolyse many peptide substrates and has various exo- and endopeptidase activities. ACE achieves this complexity by containing two homologous catalytic domains (N- and C-domains), which exhibit different substrate specificities. Here, we present the first open conformation structures of ACE N-domain and a unique closed C-domain structure (2.0 Å) where the C terminus of a symmetry-related molecule is observed inserted into the active-site cavity and binding to the zinc ion. The open native N-domain structure (1.85 Å) enables comparison with ACE2, a homologue previously observed in open and closed states. An open S 2 _S'-mutant N-domain structure (2.80 Å) includes mutated residues in the S 2 and S' subsites that effect ligand binding, but are distal to the binding site. Analysis of these structures provides important insights into how structural features of the ACE domains are able to accommodate the wide variety of substrates and allow different peptidase activities. DATABASE: The atomic coordinates and structure factors for Open nACE, Open S2_S'-nACE and Native G13-cACE structures have been deposited with codes 6ZPQ, 6ZPT and 6ZPU, respectively, in the RCSB Protein Data Bank, www.pdb.org.


  • Organizational Affiliation

    Department of Biology and Biochemistry, University of Bath, Bath, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Angiotensin-converting enzyme
A, B, C, D
629Homo sapiensMutation(s): 16 
Gene Names: ACEDCPDCP1
EC: 3.2.1 (PDB Primary Data), 3.4.15.1 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P12821 (Homo sapiens)
Explore P12821 
Go to UniProtKB:  P12821
PHAROS:  P12821
GTEx:  ENSG00000159640 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP12821
Glycosylation
Glycosylation Sites: 2Go to GlyGen: P12821-1
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose
F, G, H
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G86851RC
GlyCosmos:  G86851RC
GlyGen:  G86851RC
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
O [auth B],
P [auth B],
W [auth C]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
BCN
Query on BCN

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BA [auth C],
HA [auth D],
I [auth A],
Q [auth B]
BICINE
C6 H13 N O4
FSVCELGFZIQNCK-UHFFFAOYSA-N
PG0
Query on PG0

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J [auth A],
K [auth A],
S [auth B]
2-(2-METHOXYETHOXY)ETHANOL
C5 H12 O3
SBASXUCJHJRPEV-UHFFFAOYSA-N
ZN
Query on ZN

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CA [auth C],
JA [auth D],
L [auth A],
T [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
AA [auth C]
FA [auth D]
GA [auth D]
IA [auth D]
R [auth B]
AA [auth C],
FA [auth D],
GA [auth D],
IA [auth D],
R [auth B],
X [auth C],
Y [auth C],
Z [auth C]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CA
Query on CA

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EA [auth C],
LA [auth D],
N [auth A],
V [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

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DA [auth C],
KA [auth D],
M [auth A],
U [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.225 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.65α = 98.631
b = 99.257β = 89.629
c = 127.98γ = 111.147
Software Package:
Software NamePurpose
PHENIXrefinement
DIALSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (MRC, United Kingdom)United KingdomMR/M026647/1

Revision History  (Full details and data files)

  • Version 1.0: 2020-10-28
    Type: Initial release
  • Version 1.1: 2021-04-14
    Changes: Database references
  • Version 1.2: 2024-01-31
    Changes: Data collection, Database references, Refinement description