8QHL

Human Angiotensin-1 converting enzyme N-domain in complex with the lactotripeptide VPP

PDB DOI: https://doi.org/10.2210/pdb8QHL/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens, Bos taurus
Expression System: Cricetulus griseus
Mutation(s): Yes

Deposited: 2023-09-08 Released: 2023-11-22
Deposition Author(s): Gregory, K.S., Cozier, G.E., Acharya, K.R.
Funding Organization(s): Biotechnology and Biological Sciences Research Council (BBSRC)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.233
R-Value Work: 0.188

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

This is version 1.2 of the entry. See complete history.

Literature

Structural insights into the inhibitory mechanism of angiotensin-I-converting enzyme by the lactotripeptides IPP and VPP.

Gregory, K.S., Cozier, G.E., Schwager, S.L.U., Sturrock, E.D., Acharya, K.R.

(2024) FEBS Lett 598: 242-251

PubMed: 37904282 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1002/1873-3468.14768
Primary Citation of Related Structures:
8QFX, 8QHL

PubMed Abstract:
Human somatic angiotensin-1-converting enzyme (sACE) is composed of a catalytic N-(nACE) and C-domain (cACE) of similar size with different substrate specificities. It is involved in the regulation of blood pressure by converting angiotensin I to the vasoconstrictor angiotensin II and has been a major focus in the development of therapeutics for hypertension. Bioactive peptides from various sources, including milk, have been identified as natural ACE inhibitors. We report the structural basis for the role of two lacototripeptides, Val-Pro-Pro and Ile-Pro-Pro, in domain-specific inhibition of ACE using X-ray crystallography and kinetic analysis. The lactotripeptides have preference for nACE due to altered polar interactions distal to the catalytic zinc ion. Elucidating the mechanism of binding and domain selectivity of these peptides also provides important insights into the functional roles of ACE.

Organizational Affiliation

Department of Life Sciences, University of Bath, UK.

Macromolecule Content

Total Structure Weight: 150.68 kDa
Atom Count: 10,738
Modelled Residue Count: 1,214
Deposited Residue Count: 1,262
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Angiotensin-converting enzyme	A [auth B], C [auth A]	628	Homo sapiens	Mutation(s): 8 Gene Names: ACE, DCP, DCP1 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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P12821
Glycosylation
Glycosylation Sites: 3	Glycosylation Focus chain A [auth B] Focus chain C [auth A]	Go to GlyGen: P12821-1
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
VAL-PRO-PRO	B [auth D], D [auth C]	3	Bos taurus	Mutation(s): 0
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	E, F	2		N-Glycosylation	Interactions Focus chain E Focus chain F Interactions & Density Focus chain E Focus chain F
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose	G	4		N-Glycosylation	Interactions Focus chain G Interactions & Density Focus chain G
Glycosylation Resources
GlyTouCan: G32152BH GlyCosmos: G32152BH GlyGen: G32152BH

Entity ID: 5
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	H	3		N-Glycosylation	Interactions Focus chain H Interactions & Density Focus chain H
Glycosylation Resources
GlyTouCan: G15407YE GlyCosmos: G15407YE GlyGen: G15407YE

Entity ID: 6
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose	I, J	2		N-Glycosylation	Interactions Focus chain I Focus chain J Interactions & Density Focus chain I Focus chain J
Glycosylation Resources
GlyTouCan: G86851RC GlyCosmos: G86851RC GlyGen: G86851RC

Small Molecules

Ligands 9 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
1PE Query on 1PE Download Ideal Coordinates CCD File SDF format, chain AA [auth A] SDF format, chain BA [auth A] MOL2 format, chain AA [auth A] MOL2 format, chain BA [auth A] mmCIF format, chain AA [auth A] mmCIF format, chain BA [auth A]	AA [auth A], BA [auth A]	PENTAETHYLENE GLYCOL C₁₀ H₂₂ O₆ JLFNLZLINWHATN-UHFFFAOYSA-N		Interactions Focus chain AA [auth A] Focus chain BA [auth A] Interactions & Density Focus chain AA [auth A] Focus chain BA [auth A]
PG4 Query on PG4 Download Ideal Coordinates CCD File SDF format, chain Q [auth B] SDF format, chain Z [auth A] MOL2 format, chain Q [auth B] MOL2 format, chain Z [auth A] mmCIF format, chain Q [auth B] mmCIF format, chain Z [auth A]	Q [auth B], Z [auth A]	TETRAETHYLENE GLYCOL C₈ H₁₈ O₅ UWHCKJMYHZGTIT-UHFFFAOYSA-N		Interactions Focus chain Q [auth B] Focus chain Z [auth A] Interactions & Density Focus chain Q [auth B] Focus chain Z [auth A]
BCN Query on BCN Download Ideal Coordinates CCD File SDF format, chain W [auth A] MOL2 format, chain W [auth A] mmCIF format, chain W [auth A]	W [auth A]	BICINE C₆ H₁₃ N O₄ FSVCELGFZIQNCK-UHFFFAOYSA-N		Interactions Focus chain W [auth A] Interactions & Density Focus chain W [auth A]
PGE Query on PGE Download Ideal Coordinates CCD File SDF format, chain S [auth B] MOL2 format, chain S [auth B] mmCIF format, chain S [auth B]	S [auth B]	TRIETHYLENE GLYCOL C₆ H₁₄ O₄ ZIBGPFATKBEMQZ-UHFFFAOYSA-N		Interactions Focus chain S [auth B] Interactions & Density Focus chain S [auth B]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain CA [auth A] SDF format, chain M [auth B] SDF format, chain P [auth B] SDF format, chain R [auth B] SDF format, chain V [auth A] SDF format, chain X [auth A] MOL2 format, chain CA [auth A] MOL2 format, chain M [auth B] MOL2 format, chain P [auth B] MOL2 format, chain R [auth B] MOL2 format, chain V [auth A] MOL2 format, chain X [auth A] mmCIF format, chain CA [auth A] mmCIF format, chain M [auth B] mmCIF format, chain P [auth B] mmCIF format, chain R [auth B] mmCIF format, chain V [auth A] mmCIF format, chain X [auth A]	CA [auth A] M [auth B] P [auth B] R [auth B] V [auth A] CA [auth A], M [auth B], P [auth B], R [auth B], V [auth A], X [auth A]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain CA [auth A] Focus chain M [auth B] Focus chain P [auth B] Focus chain R [auth B] Focus chain V [auth A] Focus chain X [auth A] Interactions & Density Focus chain CA [auth A] Focus chain M [auth B] Focus chain P [auth B] Focus chain R [auth B] Focus chain V [auth A] Focus chain X [auth A]
ZN (Subject of Investigation/LOI) Query on ZN Download Ideal Coordinates CCD File SDF format, chain K [auth B] SDF format, chain T [auth A] MOL2 format, chain K [auth B] MOL2 format, chain T [auth A] mmCIF format, chain K [auth B] mmCIF format, chain T [auth A]	K [auth B], T [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain K [auth B] Focus chain T [auth A] Interactions & Density Focus chain K [auth B] Focus chain T [auth A]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain N [auth B] SDF format, chain O [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] mmCIF format, chain N [auth B] mmCIF format, chain O [auth B]	N [auth B], O [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain N [auth B] Focus chain O [auth B] Interactions & Density Focus chain N [auth B] Focus chain O [auth B]
CL (Subject of Investigation/LOI) Query on CL Download Ideal Coordinates CCD File SDF format, chain L [auth B] SDF format, chain U [auth A] MOL2 format, chain L [auth B] MOL2 format, chain U [auth A] mmCIF format, chain L [auth B] mmCIF format, chain U [auth A]	L [auth B], U [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain L [auth B] Focus chain U [auth A] Interactions & Density Focus chain L [auth B] Focus chain U [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain Y [auth A] MOL2 format, chain Y [auth A] mmCIF format, chain Y [auth A]	Y [auth A]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain Y [auth A] Interactions & Density Focus chain Y [auth A]