7NBC

Crystal structure of human serine racemase in complex with DSiP fragment Z2856434779, XChem fragment screen.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.71 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.174 

Starting Model: experimental
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Ligand Structure Quality Assessment 


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 8 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PLP
Query on PLP

Download Ideal Coordinates CCD File 
AA [auth CCC],
E [auth AAA],
IA [auth DDD],
S [auth BBB]
PYRIDOXAL-5'-PHOSPHATE
C8 H10 N O6 P
NGVDGCNFYWLIFO-UHFFFAOYSA-N
BP4 (Subject of Investigation/LOI)
Query on BP4

Download Ideal Coordinates CCD File 
EA [auth CCC]biphenyl-4-ylacetic acid
C14 H12 O2
QRZAKQDHEVVFRX-UHFFFAOYSA-N
PG0
Query on PG0

Download Ideal Coordinates CCD File 
DA [auth CCC]2-(2-METHOXYETHOXY)ETHANOL
C5 H12 O3
SBASXUCJHJRPEV-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
BA [auth CCC]
F [auth AAA]
G [auth AAA]
HA [auth CCC]
J [auth AAA]
BA [auth CCC],
F [auth AAA],
G [auth AAA],
HA [auth CCC],
J [auth AAA],
M [auth AAA],
N [auth AAA],
T [auth BBB],
W [auth BBB],
Y [auth BBB]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
FA [auth CCC]
GA [auth CCC]
K [auth AAA]
L [auth AAA]
MA [auth DDD]
FA [auth CCC],
GA [auth CCC],
K [auth AAA],
L [auth AAA],
MA [auth DDD],
NA [auth DDD],
OA [auth DDD],
PA [auth DDD],
X [auth BBB],
Z [auth BBB]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
CA [auth CCC]
H [auth AAA]
JA [auth DDD]
O [auth AAA]
U [auth BBB]
CA [auth CCC],
H [auth AAA],
JA [auth DDD],
O [auth AAA],
U [auth BBB],
V [auth BBB]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
I [auth AAA],
KA [auth DDD]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
LA [auth DDD],
P [auth AAA],
Q [auth AAA],
R [auth AAA]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.71 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.174 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.15α = 90
b = 154.86β = 98.08
c = 85.48γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DIALSdata reduction
Aimlessdata scaling
MOLREPphasing

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 Kingdom--

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