6ZUJ

Human serine racemase holoenzyme from 20% DMSO soak (XChem crystallographic fragment screen).


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.179 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Tyrosine 121 moves revealing a ligandable pocket that couples catalysis to ATP-binding in serine racemase.

Koulouris, C.R.Gardiner, S.E.Harris, T.K.Elvers, K.T.Mark Roe, S.Gillespie, J.A.Ward, S.E.Grubisha, O.Nicholls, R.A.Atack, J.R.Bax, B.D.

(2022) Commun Biol 5: 346-346

  • DOI: https://doi.org/10.1038/s42003-022-03264-5
  • Primary Citation of Related Structures:  
    6ZSP, 6ZUJ, 7NBC, 7NBD, 7NBF, 7NBG, 7NBH

  • PubMed Abstract: 

    Human serine racemase (hSR) catalyses racemisation of L-serine to D-serine, the latter of which is a co-agonist of the NMDA subtype of glutamate receptors that are important in synaptic plasticity, learning and memory. In a 'closed' hSR structure containing the allosteric activator ATP, the inhibitor malonate is enclosed between the large and small domains while ATP is distal to the active site, residing at the dimer interface with the Tyr121 hydroxyl group contacting the α-phosphate of ATP. In contrast, in 'open' hSR structures, Tyr121 sits in the core of the small domain with its hydroxyl contacting the key catalytic residue Ser84. The ability to regulate SR activity by flipping Tyr121 from the core of the small domain to the dimer interface appears to have evolved in animals with a CNS. Multiple X-ray crystallographic enzyme-fragment structures show Tyr121 flipped out of its pocket in the core of the small domain. Data suggest that this ligandable pocket could be targeted by molecules that inhibit enzyme activity.


  • Organizational Affiliation

    Sussex Drug Discovery Centre, University of Sussex, Brighton, BN1 9QG, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine racemaseA [auth AAA],
B [auth BBB],
C [auth CCC],
D [auth DDD]
346Homo sapiensMutation(s): 2 
Gene Names: SRR
EC: 5.1.1.18 (PDB Primary Data), 4.3.1.18 (PDB Primary Data), 4.3.1.17 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q9GZT4 (Homo sapiens)
Explore Q9GZT4 
Go to UniProtKB:  Q9GZT4
PHAROS:  Q9GZT4
GTEx:  ENSG00000167720 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9GZT4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PGE
Query on PGE

Download Ideal Coordinates CCD File 
DA [auth CCC],
E [auth AAA],
GA [auth DDD],
NA [auth DDD],
V [auth CCC]
TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
AA [auth CCC],
CA [auth CCC],
N [auth AAA],
U [auth CCC]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
F [auth AAA],
HA [auth DDD]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
BA [auth CCC]
IA [auth DDD]
J [auth AAA]
JA [auth DDD]
K [auth AAA]
BA [auth CCC],
IA [auth DDD],
J [auth AAA],
JA [auth DDD],
K [auth AAA],
KA [auth DDD],
L [auth AAA],
LA [auth DDD],
M [auth AAA],
MA [auth DDD],
Q [auth BBB],
X [auth CCC],
Y [auth CCC],
Z [auth CCC]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
FA [auth DDD],
H [auth AAA],
R [auth BBB],
W [auth CCC]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
G [auth AAA]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
EA [auth DDD]
I [auth AAA]
O [auth AAA]
P [auth AAA]
S [auth BBB]
EA [auth DDD],
I [auth AAA],
O [auth AAA],
P [auth AAA],
S [auth BBB],
T [auth BBB]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
LLP
Query on LLP
A [auth AAA],
B [auth BBB],
C [auth CCC],
D [auth DDD]
L-PEPTIDE LINKINGC14 H22 N3 O7 PLYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.179 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.062α = 90
b = 154.998β = 98.26
c = 85.652γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DIALSdata reduction
Aimlessdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2021-03-03
    Type: Initial release
  • Version 1.1: 2022-04-27
    Changes: Database references
  • Version 1.2: 2022-05-04
    Changes: Structure summary
  • Version 1.3: 2024-01-31
    Changes: Data collection, Database references, Derived calculations, Refinement description