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- EMDB-52439: PSMA without nanobody -

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Open data


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Basic information

Entry
Database: EMDB / ID: EMD-52439
TitlePSMA without nanobody
Map dataPSMA
Sample
  • Complex: Glutamate carboxypeptidase 2 (PSMA)
    • Protein or peptide: Glutamate carboxypeptidase 2
KeywordsGlutamate carboxypeptidase 2 / MEMBRANE PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.45 Å
AuthorsZalk R / Alon G / Papo N / Zarivach R
Funding support Israel, United States, United Kingdom, 6 items
OrganizationGrant numberCountry
Other private846497 Israel
United States - Israel Binational Science Foundation (BSF)2019303 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM144393 United States
Rosetrees TrustOoR2022/100004 United Kingdom
Israel Science Foundation1615/19 Israel
Worldwide Cancer Research20-0238 United Kingdom
CitationJournal: Int J Biol Macromol / Year: 2025
Title: Structural analysis of nanobody interactions with their prostate-specific membrane antigen binding epitopes.
Authors: Gal Alon-Zchut / Ran Zalk / Truc T Huynh / Michael R Zalutsky / Yossi Weizmann / Raz Zarivach / Niv Papo /
Abstract: Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, is a promising target for diagnostics and therapy. However, the monoclonal antibodies in current use for PSMA targeting ...Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, is a promising target for diagnostics and therapy. However, the monoclonal antibodies in current use for PSMA targeting and inhibition have suboptimal activities due to their poor tissue and cell penetration and slow normal tissue clearance. Potentially superior alternatives are nanobodies (NBs), the single-chain variable domains of heavy-chain antibodies derived from camelids. The advantages of NBs include small size (~15 kDa), ability to bind hidden epitopes, and rapid clearance. In contrast to most known PSMA inhibitors, which bind to the same catalytic site in PMSA, NBs can bind to different PSMA epitopes, facilitating heterovalent binding strategies that could enhance their therapeutic and diagnostic potential. The objective of this study was to map these binding epitopes and hence to acquire an atomic-resolution understanding of NB-PMSA binding by investigating the structural interactions between PSMA and three NBs (NB7, NB8, and NB37). Using cryo-electron microscopy to generate high-resolution structures of NB-PSMA complexes, we found that NB7 had the highest affinity for PSMA due to a larger interface and to stabilizing interactions, including salt bridges and π-π stacking. Notably, we also found that NB7 and NB8 can bind simultaneously to different PSMA epitopes without interfering with the function of PSMA (which is still not completely known), opening the way for the development of theranostic applications for prostate cancer treatment and imaging. Importantly, NB7 binds specifically to human PSMA but not to murine PSMA, due to key amino acid differences responsible for its species specificity.
History
DepositionDec 31, 2024-
Header (metadata) releaseJul 16, 2025-
Map releaseJul 16, 2025-
UpdateJul 16, 2025-
Current statusJul 16, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_52439.png

Downloads & links

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Map

FileDownload / File: emd_52439.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationPSMA
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.89 Å/pix.
x 256 pix.
= 227.84 Å		0.89 Å/pix.
x 256 pix.
= 227.84 Å		0.89 Å/pix.
x 256 pix.
= 227.84 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.89 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.20859398 - 0.35603455
Average (Standard dev.)0.00025392213 (±0.012198993)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 227.84 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: PSMA halfB

Fileemd_52439_half_map_1.map
AnnotationPSMA halfB
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: PSMA halfA

Fileemd_52439_half_map_2.map
AnnotationPSMA halfA
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Glutamate carboxypeptidase 2 (PSMA)

EntireName: Glutamate carboxypeptidase 2 (PSMA)
Components
  • Complex: Glutamate carboxypeptidase 2 (PSMA)
    • Protein or peptide: Glutamate carboxypeptidase 2

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Supramolecule #1: Glutamate carboxypeptidase 2 (PSMA)

SupramoleculeName: Glutamate carboxypeptidase 2 (PSMA) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 170 MDa

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Macromolecule #1: Glutamate carboxypeptidase 2

MacromoleculeName: Glutamate carboxypeptidase 2 / type: protein_or_peptide / ID: 1 / Details: Missing the TM domain / Enantiomer: LEVO / EC number: glutamate carboxypeptidase II
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MWNLLHETDS AVATARRPRW LCAGALVLAG GFFLLGFLFG WFIKSSNEAT NITPKHNMKA FLDELKAEN IKKFLYNFTQ IPHLAGTEQN FQLAKQIQSQ WKEFGLDSVE LAHYDVLLSY P NKTHPNYI SIINEDGNEI FNTSLFEPPP PGYENVSDIV PPFSAFSPQG ...String:
MWNLLHETDS AVATARRPRW LCAGALVLAG GFFLLGFLFG WFIKSSNEAT NITPKHNMKA FLDELKAEN IKKFLYNFTQ IPHLAGTEQN FQLAKQIQSQ WKEFGLDSVE LAHYDVLLSY P NKTHPNYI SIINEDGNEI FNTSLFEPPP PGYENVSDIV PPFSAFSPQG MPEGDLVYVN YA RTEDFFK LERDMKINCS GKIVIARYGK VFRGNKVKNA QLAGAKGVIL YSDPADYFAP GVK SYPDGW NLPGGGVQRG NILNLNGAGD PLTPGYPANE YAYRRGIAEA VGLPSIPVHP IGYY DAQKL LEKMGGSAPP DSSWRGSLKV PYNVGPGFTG NFSTQKVKMH IHSTNEVTRI YNVIG TLRG AVEPDRYVIL GGHRDSWVFG GIDPQSGAAV VHEIVRSFGT LKKEGWRPRR TILFAS WDA EEFGLLGSTE WAEENSRLLQ ERGVAYINAD SSIEGNYTLR VDCTPLMYSL VHNLTKE LK SPDEGFEGKS LYESWTKKSP SPEFSGMPRI SKLGSGNDFE VFFQRLGIAS GRARYTKN W ETNKFSGYPL YHSVYETYEL VEKFYDPMFK YHLTVAQVRG GMVFELANSI VLPFDCRDY AVVLRKYADK IYSISMKHPQ EMKTYSVSFD SLFSAVKNFT EIASKFSERL QDFDKSNPIV LRMMNDQLM FLERAFIDPL GLPDRPFYRH VIYAPSSHNK YAGESFPGIY DALFDIESKV D PSKAWGEV KRQIYVAAFT VQAAAETLSE VA

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 30.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm
Sample stageCooling holder cryogen: NITROGEN

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Image processing

CTF correctionType: NONE
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.45 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 46457
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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