HMM analysis could be one solution, but are there any good programs?
The best approach is to look for functional motifs associated with active site features and activity. Try using a tool like psi blast - http://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Web&PAGE=Proteins&PROGRAM=blastp&RUN_PSIBLAST=on
You can also use ScanProsite tool (http://prosite.expasy.org/scanprosite/ ) to scan for a specific motif.
Other tools you may use are:
http://supfam.cs.bris.ac.uk/SUPERFAMILY/
http://smart.embl-heidelberg.de/smart/set_mode.cgi?NORMAL=1
PS. you can try EnzymeDetector from BRENDA (http://edbs.tu-bs.de/)
Try PeptidePatternRecognition
http://vbn.aau.dk/en/publications/peptide-pattern-recognition(1400c5df-fa69-4701-8d67-ec5c38cc963b).html
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