PXD028851

PXD028851 is an original dataset announced via ProteomeXchange.

Title	A substrate-like thrombin inhibitor from the saliva of the flea Xenopsylla cheopis is resistant to cleavage by the enzyme
Description	XC-43 is a small peptide identified in the sialome of the flea Xenopsylla cheopis and act as a fast, tight-binding inhibitor of thrombin with a dissociation constant of less than 10 pM. The crystal structure of XC-43 in complex with thrombin shows that despite its substrate-like binding mode, XC-43 is not detectably cleaved by thrombin and that it interacts with the thrombin surface from the enzyme catalytic site through the fibrinogen-binding exosite I. The low rate of hydrolysis is verified in solution experiments with XC-43 which show the substrate to be largely intact after two hours of incubation with thrombin at 37°C. The potential of XC-43 as an anticoagulant is suggested by increased arterial occlusion time, tail bleeding time, and blood coagulation parameters in rat models of thrombosis.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_15:50:20.919.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephen Lu
SpeciesList	scientific name: Xenopsylla cheopis; NCBI TaxID: 163159;
ModificationList	reduction of disulfide crosslink in cystine to two cysteines; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-29 13:59:19	ID requested
⏵ 1	2022-02-16 15:50:21	announced

Lu S, Tirloni L, Oliveira MB, Bosio CF, Nardone GA, Zhang Y, Hinnebusch BJ, Ribeiro JM, Andersen JF, Identification of a substrate-like cleavage-resistant thrombin inhibitor from the saliva of the flea Xenopsylla cheopis. J Biol Chem, 297(5):101322(2021) [pubmed]

submitter keyword: Blood feeding, X-ray crystallography, flea, thrombin

Jose M.C. Ribeiro
contact affiliation	Laboratory of Malaria and Vector Research, NIAID, NIH
contact email	JRIBEIRO@niaid.nih.gov
lab head
Stephen Lu
contact affiliation	NIH/NIAID
contact email	stephen.lu@nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028851
     1. Label: PRIDE project
     2. Name: A substrate-like thrombin inhibitor from the saliva of the flea Xenopsylla cheopis is resistant to cleavage by the enzyme